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The role of cell-free dna in non-invasive diagnosis of urinary tract infection

UroPrecision 2024年第2期2卷 41-50页

作者： Yu Zhao Wenhui Zhang Yina Ma Xin Zhang Department of Urology Surgery Beijing Chao-Yang Hospital Affiliated to Capital Medical UniversityBeijingChina Department of Hepatobiliary Surgery Beijing Chao‐Yang Hospital Affiliated to Capital Medical UniversityBeijingChina

Urinary tract infection(UTI)constitutes a pervasive health *** are dichotomously classified into upper and lower strata,and further categorized as either complicated or *** UTIs predominantly afflict the renal and ureteral domains,typified by conditions exemplified in pyelonephritis,whereas lower UTIs manifest within the confines of the urethra and *** conventional diagnosis of UTIs relies upon clinical manifestations and urine *** symptoms encompass dysuria,frequent micturition,hematuria,and suprapubic *** culture serves to identify the specific pathogens instigating the infection and assess their antibiotic ***,this procedural protocol generally necessitates an approximate duration of 24 h,coupled with an additional 24-h interval for antibiotic susceptibility *** contradistinction,the detection of cell-free dna(cfdna)in the circulatory system presents a potential avenue for non-invasive diagnostic ***,cfdna emanates from deteriorating cells,affording insights into the extant cellular demise within the *** scholarly inquiry has established a positive correlation between cfdna concentration in the bloodstream and the incidence of cell death in conditions,such as severe traumas,sepsis,aseptic inflammation,myocardial infarction,and ***,limited investigative effort has been devoted to elucidating the diagnostic potential of cfdna in the context of ***,the concentration and constitution of plasma cfdna harbor substantial promise for non-invasively diagnosing *** summation,the utilization of cfdna in UTI diagnosis remains an incipient area of scholarly pursuit,underscoring the imperative for further research to elucidate the prospective role of plasma cfdna in non-intrusively discerning UTIs.

关键词： cell-free dna diagnosis dna methylation urinary tract infection

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cell-free dna in the management of prostate cancer:Current status and future prospective

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Asian Journal of Urology 2023年第3期10卷 298-316页

作者： Wei He Yutian Xiao Shi Yan asheng Zhu Shancheng Ren College of Basic Medical Sciences Naval Medical UniversityShanghaiChina Department of Urology The First Affiliated HospitalNaval Medical UniversityShanghaiChina Department of Urology Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Urology The Second Affiliated HospitalNaval Medical UniversityShanghaiChina

Objective:With the escalating prevalence of prostate cancer(PCa)in China,there is an urgent demand for novel diagnostic and therapeutic *** investigations have been conducted on the clinical implementation of circulating free dna(cfdna)in *** review aims to provide a comprehensive overview of the present state of cfdna as a biomarker for PCa and to examine its merits and obstacles for future clinical ***:Relevant peer-reviewed manuscripts on cfdna as a PCa marker were evaluated by PubMed search(2010-2022)to evaluate the roles of cfdna in PCa diagnosis,prognosis,and prediction,***:cfdna is primarily released from cells undergoing necrosis and apoptosis,allowing for non-invasive insight into the genomic,transcriptomic,and epigenomic alterations within various PCa disease ***-generation sequencing,among other detection methods,enables the assessment of cfdna abundance,mutation status,fragment characteristics,and epigenetic *** analysis based on cfdna can facilitate early detection of PCa,risk stratification,and treatment ***,standardization of cfdna detection methods is still required to expedite its clinical ***:cfdna provides a non-invasive,rapid,and repeatable means of acquiring multidimensional information from PCa patients,which can aid in guiding clinical decisions and enhancing patient *** the application barriers of cfdna necessitates increased data sharing and international collaboration.

关键词： cell-free dna Biomarker Early detection Prognosis Prostate cancer

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The protein corona modulates the inflammation inhibition by cationic nanoparticles via cell-free dna scavenging

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Bioactive Materials 2022年第7期7卷 249-259页

作者： Xingliang Liu Huiyi Liang Yanzi Yan Jingjiao Wu Massimo Bottini Lixin Liu Yongming Chen School of Materials Science and Engineering Key Laboratory for Polymeric Composite and Functional Materials of Ministry of EducationSun Yat-sen UniversityGuangzhou510275China Department of Experimental Medicine University of Rome Tor VergataRome00133Italy

A central paradigm in nanomedicine is that when synthetic nanoparticles(NPs)enter the body,they are immediately cloaked by a corona of macromolecules(mostly proteins)that mediates the role of the physico-chemical properties in the NP biological functions(the“coronation paradigm”).In this work,we focused on the assessment of the“coronation paradigm”for cationic NPs(cNPs)used as rheumatoid arthritis(RA)drugs due to their ability to scavenge cell-free dna(cfdna).We fabricated series of cNPs uniformly coated with single or di-hydroxyl groups and different types of amino groups and showed that hydroxylated nanoparticles displayed a prolonged retention in inflamed joints and greater anti-inflammatory effect in collagen-induced arthritis(CIA)rats than the non-hydroxylated ***,the cNPs with secondary amines and a di-hydroxyl shell showed the best performance among the tested *** analysis showed that the cNPs with a di-hydroxyl shell adsorbed less opsonin proteins than the cNPs carrying mono hydroxyl groups and non-hydroxylated ones,which may provide a mechanistic explanation for the different biodistribution profiles of ***,this study suggests that the protein corona mediates the effects of the surface chemistry on the fate and functions of cNPs as anti-RA drugs.

关键词： Cationic nanoparticles cell-free dna Inflammation inhibition Protein corona Rheumatoid arthritis

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Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free dna for rheumatoid arthritis therapy

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Bioactive Materials 2022年第12期7卷 409-420页

作者： Ying Chen Yonglin Wang Xianfang Jiang Jinhong Cai Yuting Chen Hanji Huang Yuan Yang Li Zheng Jinmin Zhao Ming Gao Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Guangxi Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Department of Orthopedics The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Department of Oral Radiology College of Stomatology of Guangxi Medical UniversityNanning530021China Guangxi Key Laboratory of Regenerative Medicine International Joint Laboratory on Regeneration of Bone and Soft TissuesThe First Affiliated Hospital of Guangxi Medical UniversityNanning530021China

Excessive cell-free dna(cfdna)released by damaged or apoptotic cells can cause inflammation,impacting the progression of rheumatoid arthritis(RA).cfdna scavengers,such as cationic nanoparticles(NPs),have been demonstrated as an efficient strategy for treating ***,most scavengers are limited by unfavorable biocompatibility and poor scavenging ***,by exploiting the favorable biocompatibility,biodegradability and bioadhesion of polydopamine(P),we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfdna for RA *** showed that DPs endowed with superior binding affinity of cfdna and little cytotoxicity,which effectively inhibited lipopolysaccharide(LPS)stimulated inflammation in vitro,resulting in the relief of joint swelling,synovial hyperplasia and cartilage destruction in RA ***,DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfdna binding affinity,leading to excellent RA therapeutic effect among all of the treated groups,which was even close to normal *** finding provides a novel strategy for the treatment of cfdna-associated diseases.

关键词： cell-free dna Polydopamine Rheumatoid arthritis Nucleic acid binding affinity Immunotherapy

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Non-invasive chromosome screening for embryo preimplantation using cell-free dna

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Reproductive and Developmental Medicine 2022年第2期6卷 113-120页

作者： Fang He Ya-Xin Yao Jing Wang Dun-Mei Zhao An-Qi Wan Jun Ren Xi Lei Center for Reproduction and Genetics Xiangtan Central HospitalXiangtan 411100HunanChina Department of Clinical Research Yikon GenomicsSuzhou 215028JiangsuChina

Preimplantation genetic testing (PGT) is a widely adopted screening method that can be performed to identify and select embryos with normal ploidy;however, PGT relies on embryo biopsy, that is, polar body, embryo cells, or trophectoderm biopsy, to obtain embryonic dna, increase its technical limitations. Studies have indicated that biopsy may have an influence on the quality and development of embryos, and increase the chance of abnormal epigenetic modifications. Therefore, non-invasive PGT (niPGT) detection of cell-free dna (cfdna) has gradually become a hot research topic in the field of assisted reproduction. Studies showed cfdna could be detected in blastocyst fluid and spent culture medium (SCM) in vitro cultured embryos. The cfdna collection requires less skill and makes lower risk to embryos. Some studies have been conducted to evaluate the feasibility of SCM-based niPGT approaches. When comparing the ploidy consistency of cfdna in SCM, its consistency to the conventional PGT for aneuploidies results fluctuated widely, it is critical to recognize the factors influencing accuracy. These contradictory results may be related to factors such as the difference in SCM sampling methods and sampling time, and the definition of consistency. In this review, we aimed to comprehensively summarize how researchers use embryonic cfdna to conduct niPGT detection. It also systematically reviews the factors affecting the accuracy of the test and its underlying issues, as well as prospective applications. We hope to provide a basis for future niPGT research and a useful reference for the standardized operation of niPGT that can be widely applied in clinical practice.

关键词： Aneuploid cell-free dna Non-invasive preimplantation genetic testing Spent culture media

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Depth of invasion to the bladder wall as a prognostic factor and its association with circulating cell-free dna levels in patients with muscle-invasive bladder cancer

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当代泌尿学（英文） 2023年第4期17卷 229-235页

作者： Yusuke lemura Makito Miyake Shinji Fukui Tomomi Fujii Sayuri Ohnishi Shunta Hori Yosuke Morizawa Yasushi Nakai Kazumasa Torimoto Nobumichi Tanaka Kiyohide Fujimoto Department of Urology Nara Medical UniversityKashiharaNaraJapan Department of Diagnostic Pathology Nara Medical UniversityKashiharaNaraJapan Department of Urology Nara Medical UniversityKashiharaNaraJapan Department of Prostate Brachytherapy Nara Medical UniversityKashiharaNaraJapan

Background:Radical cystectomy(RC)is the standard surgical treatment for patients with muscle-invasive bladder cancer,but the prognosis is not favorable,and new prognostic factors need to be *** investigated the potential of depth of invasion(DOI)as a prognostic factor in patients with muscle-invasive bladder cancer who underwent ***,we examined the asso-ciation between preoperative levels of circulating cell-free dna and DOI.Materials and methods:We retrospectively reviewed patients who underwent RC between January 2007 and December 2017;those who received neoadjuvant chemotherapy were *** of invasion was measured using hematoxylin-eosin-stained RC specimens.Results:Of the 121 patients selected,41(33.9％)were eligible for *** median follow-up period was 14 months and mean DOI was 17 mm(range,2-75 mm).Long DOI(＞17 mm)was significantly associated with shorter progression-free survival(hazard ratio,14.5;95％confidence interval,3.9-53.97,p＜0.0001)and cancer-specific survival(hazard ratio,18.97;95％confidence interval,4.04-88.99,p=0.0002)compared with short *** analysis revealed that DOI was an independent risk factor for cancer-specific *** levels of circulating cell-free dna were significantly higher in patients with a longer DOI than in those with short DOI(65 vs.20 ng/mL,respectively;p=0.028).Conclusions:Depth of invasion predicted with levels of circulating cell-free dna and thus could be a useful prognostic factor.

关键词： Bladder cancer cell-free dna Depth of invasion

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cell-free dna liquid biopsy for early detection of gastrointestinal cancers:A systematic review

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1799-1812页

作者： Isabelle Uhe Monika Elisabeth Hagen Frederic Ris Jeremy Meyer Christian Toso Jonathan Douissard Abdominal Surgery Division Geneva University HospitalsGeneva 1211Switzerland

BACKGROUND Gastrointestinal tumors are among the most common cancer types,and early detection is paramount to improve their ***-free dna(cfdna)liquid biopsy raises significant hopes for non-invasive early *** To describe current applications of this technology for gastrointestinal cancer detection and *** A systematic review of the literature was performed across the PubMed *** reporting the use of cfdna liquid biopsy in the screening or diagnosis of gastrointestinal cancers were included in the *** A total of 263 articles were screened for eligibility,of which 13 articles were *** investigated colorectal cancer(5 studies),pancreatic cancer(2 studies),hepatocellular carcinoma(3 studies),and multi-cancer detection(3 studies),including gastric,oesophageal,or bile duct cancer,representing a total of 4824 *** sensitivities ranged from 71% to 100%,and specificities ranged from 67.4% to 100%.Pre-cancerous lesions detection was less performant with a sensitivity of 16.9% and a 100% specificity in one *** study using a large biobank demonstrated a 94.9% sensitivity in detecting cancer up to 4 years before clinical symptoms,with a 61% accuracy in tissue-of-origin *** cfdna liquid biopsy seems capable of detecting gastrointestinal cancers at an early stage of development in a non-invasive and repeatable manner and screening simultaneously for multiple cancer types in a single blood *** trials in clinically relevant settings are required to determine the exact place of this technology in gastrointestinal cancer screening and diagnosis strategies.

关键词： cell-free dna Tumor dna Liquid biopsy Next-generation sequencing Cancer genomics Pancreatic cancer Colorectal cancer Hepatocellular carcinoma Multicancer detection Cancer screening Public health Precision oncology

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5-Hydroxymethylome in Circulating cell-free dna as A Potential Biomarker for Non-small-cell Lung Cancer

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Genomics, Proteomics & Bioinformatics 2018年第3期16卷 187-199页

作者： Ji Zhang Xiao Han Chunchun Gao Yurong Xing Zheng Qi Ruijuan Liu Yueqin Wang Xiaojian Zhang Yun-Gui Yang Xiangnan Li Baofa Sun Xin Tian Department of Pharmacy The First Affiliated Hospital of Zhengzhou University Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou University Sino-Danish College University of Chinese Academy of Sciences Physical Examination Center The First Affiliated Hospital of Zhengzhou University Department of Anesthesiology The First Affiliated Hospital of Zhengzhou University CAS Key Laboratory of Genomic and Precision Medicine School of Future Technology Beijing Institute of GenomicsChinese Academy of Sciences Institute of Stem cell and Regeneration Chinese Academy of Sciences Department of Thoracic Surgery The First Affiliated Hospital of Zhengzhou University

Non-small-cell lung cancer （NSCLC）, the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymetbylcytosine （ShmC） signatures in circulating cell-free dna （cfdna） that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminat- ing tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfdna of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identi- fied six potential biomarkers from 66 patients and 67 healthy controls （mean decrease accuracy 〉 3.2, P 〈 3.68E-19） using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient＇s cfdna identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.

关键词： 5-Hydroxymethylcytosine Lung cancer cell-free dna Biomarker 5hmC-Seal

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Quick recovery and characterization of cell-free dna in seminal plasma of normozoospermia and azoospermia： implications for non-invasive genetic utilities

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Asian Journal of Andrology 2009年第6期11卷 703-709页

作者： Hong-Gang Li Shi-Yun Huang Hui Zhou Ai-Hua Liao Cheng-Liang Xiong Family Planning Research Institute and Centre for Reproductive Medicine Tongji Medical College Huazhong Universityof Science and Technology Wuhan 430030 China

We established a quick and reliable method for recovering cell-free seminal dna （cfsdna）, by using the binding-washing-elution procedure on the dna purification column. Low variations （below 15%） among the triplicate values of cfsdna quantity verified the reproducibility of our cfsdna recovery method. Similar cfsdna yield and size distribution between seminal plasma acquired by filtration and centrifugation confirmed the presence of cfsdna. To investigate the general characterization of cfsdna, the quantitation and size distribution of cfsdna from normozoospermic and azoospermic semen were analyzed by real-time PCR and electrophoresis, respectively. Cfsdna concentration in semen with normozoospermia （n = 11） was 1.34 ± 0.65 μg ·mL^-1, whereas a higher cfsdna concentration was observed in azoospermia （2.56 ± 1.43 μg ·mL^-1, n = 9）. The continuous distribution of dna fragments ranging from -1 kb to 15 kb and a spectrum of multiples of 180-bp fragments were observed in each normozoospermic and azoospermic sample. Distinct characteristic dna ladder fragmentations in some azoospermic samples implicated that cfsdna originate partly from apoptotic cells. Cfsdnas of 36 selected azoospermic patients with known information of Y chromosome microdeletion were subjected to the same microdeletion analysis by multiplex PCR and PCR amplification of sY114 （1 450 bp）. All multiplex PCR reactions with cfsdna amplified successfully and provided the same result as leukocyte dna. PCR amplification of sY114 gave a 1 450-bp amplicon as expected. Our data suggested the potential use of cfsdna in search of biomarker or diagnostic procedures.

关键词： azoospermia cell-free dna normozoospermia seminal plasma Y chromosome microdeletion

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Clinical Value of Peripheral Blood Circulating Tumor cells and cell-free dna Combined Detection in Triple-Negative Breast Cancer

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Proceedings of Anticancer Research 2022年第3期6卷 69-73页

作者： Jirui Sun Shuangqiu Ma Hong Chen Huijuan Geng Jinku Zhang Department of Pathology Baoding First Central HospitalBaoding 071000China Department of Clinical Medicine Baoding People's HospitalBaoding 071051China

Objective:To determine the clinical value of combined detection of circulating tumor cells(CTCs)and cell-free dna(cfdna)in peripheral blood of patients with triple-negative breast ***:41 patients with breast cancer admitted to the First Central Hospital of Baoding from January 2020 to December 2021 were selected and recruited into the experimental group,42 patients with benign breast cancer admitted during the same period were recruited into the conditional control group,and 41 healthy patients admitted during the same period were recruited into the blank control *** positive rate of peripheral blood CTCs,the level of cfdna,and the diagnostic efficacy of peripheral blood CTCs,cfdna alone and the combination thereof for breast cancer were ***:The positive rates of peripheral blood CTCs in the experimental group,the conditional control group,and the blank control group were 43.90%,11.90%,and 9.74%,respectively,and there was significant difference among the *** levels of cfdna in peripheral blood of the experimental group,the conditional control group,and the blank control group were 0.26±0.08 bp,0.17±0.03 bp,and 0.15±0.04 bp,respectively,which were statistically *** detection levels of 100 bp hTERT/ng mT1 and 241 bp hTERT/ng-mT1 in the experimental group were significantly higher than those in the conditional control group and the blank control *** accuracy of peripheral blood CTCs detection in the three groups was 66.21%,the accuracy of cfDA241 bp/100 hp hTERT detection was 80.41%,and the accuracy of combined detection of peripheral blood CTCs and cfdna was 94.03%.Conclusion:The clinical application of peripheral blood CTCs combined with cfdna level detection can increase detection accuracy,provide data support for clinicians,and improve the clinical diagnostic effect of triple-negative breast cancer.

关键词： Peripheral blood circulating tumor cells cell-free dna Triple-negative breast cancer

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