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Nucleic Acids Research Jun 2021
Topics: DNA; DNA-Binding Proteins; Single Molecule Imaging
PubMed: 34153108
DOI: 10.1093/nar/gkab497 -
Molecules (Basel, Switzerland) May 2023Precise control of the structure of metallic nanomaterials is critical for the advancement of nanobiotechnology. As DNA (deoxyribonucleic acid) can readily modify... (Review)
Review
Precise control of the structure of metallic nanomaterials is critical for the advancement of nanobiotechnology. As DNA (deoxyribonucleic acid) can readily modify various moieties, such as sulfhydryl, carboxyl, and amino groups, using DNA as a directing ligand to modulate the morphology of nanomaterials is a promising strategy. In this review, we focus on the use of DNA as a template to control the morphology of metallic nanoparticles and their biomedical applications, discuss the use of DNA for the metallization of gold and silver, explore the factors that influence the process, and outline its biomedical applications. This review aims to provide valuable insights into the DNA-guided growth of nanomaterials. The challenges and future directions are also discussed.
Topics: Nanostructures; Gold; Silver; DNA
PubMed: 37175332
DOI: 10.3390/molecules28093922 -
BMC Nephrology Oct 2019Cell-free deoxyribonucleic acid DNA (cf-DNA) in urine is promising due to the advantage of urine as an easily obtained and non-invasive sample source over tissue and...
INTRODUCTION
Cell-free deoxyribonucleic acid DNA (cf-DNA) in urine is promising due to the advantage of urine as an easily obtained and non-invasive sample source over tissue and blood. In clinical practice, it is important to identify non-invasive biomarkers of chronic kidney disease (CKD) in monitoring and surveillance of disease progression. Information is limited, however, regarding the relationship between urine and plasma cf-DNA and the renal outcome in CKD patients.
METHODS
One hundred and thirty-one CKD patients were enrolled between January 2016 and September 2018. Baseline urine and plasma cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) were isolated using quantitative real-time PCR. Estimated glomerular filtration rate (eGFR) measurement was performed at baseline and 6-month follow-up. Favorable renal outcome was defined as eGFR at 6 months minus baseline eGFR> = 0. Receiver operator characteristics (ROC) curve analysis was performed to assess different samples of cf-DNA to predict favorable renal outcomes at 6 months. A multivariate linear regression model was used to evaluate independent associations between possible predictors and different samples of cf-DNA.
RESULTS
Patients with an advanced stage of CKD has significantly low plasma cf-nDNA and high plasma neutrophil gelatinase-associated lipocalin (NGAL) levels. Low urine cf-mtDNA, cf-nDNA levels and low plasma NGAL were significantly correlated with favorable renal outcomes at 6 months. The urine albumin-creatinine ratio (ACR) or urine protein-creatinine ratio (PCR) level is a robust predictor of cf-mtDNA and cf-nDNA in CKD patients. Baseline urine levels of cf-mtDNA and cf-nDNA could predict renal outcomes at 6 months.
CONCLUSIONS
Urinary cf-mtDNA and cf-nDNA may provide novel prognostic biomarkers for renal outcome in CKD patients. The levels of plasma cf-nDNA and plasma NGAL are significantly correlated with the severity of CKD.
Topics: Adult; Aged; Albuminuria; Area Under Curve; Biomarkers; Cell-Free Nucleic Acids; Creatinine; DNA, Mitochondrial; Disease Progression; Female; Glomerular Filtration Rate; Humans; Lipocalin-2; Male; Middle Aged; Predictive Value of Tests; Prognosis; ROC Curve; Renal Insufficiency, Chronic
PubMed: 31660901
DOI: 10.1186/s12882-019-1549-x -
Molecules (Basel, Switzerland) Nov 2019DNA-templated fluorescent nanoclusters (NCs) have attracted increasing research interest on account of their prominent features, such as DNA sequence-dependent... (Review)
Review
DNA-templated fluorescent nanoclusters (NCs) have attracted increasing research interest on account of their prominent features, such as DNA sequence-dependent fluorescence, easy functionalization, wide availability, water solubility, and excellent biocompatibility. Coupling DNA templates with complementary DNA, aptamers, G-quadruplex, and so on has generated a large number of sensors. Additionally, the preparation and applications of DNA-templated fluorescent NCs in these sensing have been widely studied. This review firstly focuses on the properties of DNA-templated fluorescent NCs, and the synthesis of DNA-templated fluorescent NCs with different metals is then discussed. In the third part, we mainly introduce the applications of DNA-templated fluorescent NCs for sensing metal ions. At last, we further discuss the future perspectives of DNA-templated fluorescent NCs in the synthesis and sensing metal ions in the environmental and biological fields.
Topics: Biosensing Techniques; DNA; DNA Replication; Fluorescence; Ions; Metals; Molecular Structure; Nanostructures
PubMed: 31752270
DOI: 10.3390/molecules24224189 -
Biomolecules Oct 2022Neutrophil extracellular traps (NETs) are net-like complexes expelled from neutrophils, composing cell-free deoxyribonucleic acid (DNA), histones, and neutrophil granule... (Review)
Review
Neutrophil extracellular traps (NETs) are net-like complexes expelled from neutrophils, composing cell-free deoxyribonucleic acid (DNA), histones, and neutrophil granule proteins. Besides capturing and eliminating pathogens, NETs also exacerbate the inflammatory response associated with various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Currently, there are growing reports about NETs involved in the pathogenesis of ocular diseases. This review primarily focuses on the pathogenesis of NETs in the ophthalmology field, highlighting their importance in serving as potential targets for the therapy of ocular diseases.
Topics: Extracellular Traps; Histones; Neutrophils; DNA; Cell-Free Nucleic Acids
PubMed: 36291649
DOI: 10.3390/biom12101440 -
The Journal of Biological Chemistry Jun 2023For cells, it is important to repair DNA damage, such as double-strand and single-strand DNA breaks, because unrepaired DNA can compromise genetic integrity, potentially... (Review)
Review
For cells, it is important to repair DNA damage, such as double-strand and single-strand DNA breaks, because unrepaired DNA can compromise genetic integrity, potentially leading to cell death or cancer. Cells have multiple DNA damage repair pathways that have been the subject of detailed genetic, biochemical, and structural studies. Recently, the scientific community has started to gain evidence that the repair of DNA double-strand breaks may occur within biomolecular condensates and that condensates may also contribute to DNA damage through concentrating genotoxic agents used to treat various cancers. Here, we summarize key features of biomolecular condensates and note where they have been implicated in the repair of DNA double-strand breaks. We also describe evidence suggesting that condensates may be involved in the repair of other types of DNA damage, including single-strand DNA breaks, nucleotide modifications (e.g., mismatch and oxidized bases), and bulky lesions, among others. Finally, we discuss old and new mysteries that could now be addressed considering the properties of condensates, including chemoresistance mechanisms.
Topics: DNA; DNA Breaks, Double-Stranded; DNA Repair; Drug Resistance, Neoplasm; DNA Breaks, Single-Stranded; Base Pair Mismatch
PubMed: 37164156
DOI: 10.1016/j.jbc.2023.104800 -
Nature Jan 2023Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence-nonspecific degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA...
Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence-nonspecific degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA following recognition of a complementary RNA target, culminating in abortive infection. Here we report structures of Cas12a2 in binary, ternary and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of 'aromatic clamp' residues that are crucial for double-stranded DNA degradation and in vivo immune system function. Our work provides a structural basis for this mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates.
Topics: CRISPR-Associated Proteins; CRISPR-Cas Systems; DNA; RNA; Enzyme Activation; Catalytic Domain; Substrate Specificity
PubMed: 36599980
DOI: 10.1038/s41586-022-05560-w -
Molecules (Basel, Switzerland) Mar 2021The predictable nature of deoxyribonucleic acid (DNA) interactions enables assembly of DNA into almost any arbitrary shape with programmable features of nanometer... (Review)
Review
The predictable nature of deoxyribonucleic acid (DNA) interactions enables assembly of DNA into almost any arbitrary shape with programmable features of nanometer precision. The recent progress of DNA nanotechnology has allowed production of an even wider gamut of possible shapes with high-yield and error-free assembly processes. Most of these structures are, however, limited in size to a nanometer scale. To overcome this limitation, a plethora of studies has been carried out to form larger structures using DNA assemblies as building blocks or tiles. Therefore, DNA tiles have become one of the most widely used building blocks for engineering large, intricate structures with nanometer precision. To create even larger assemblies with highly organized patterns, scientists have developed a variety of structural design principles and assembly methods. This review first summarizes currently available DNA tile toolboxes and the basic principles of lattice formation and hierarchical self-assembly using DNA tiles. Special emphasis is given to the forces involved in the assembly process in liquid-liquid and at solid-liquid interfaces, and how to master them to reach the optimum balance between the involved interactions for successful self-assembly. In addition, we focus on the recent approaches that have shown great potential for the controlled immobilization and positioning of DNA nanostructures on different surfaces. The ability to position DNA objects in a controllable manner on technologically relevant surfaces is one step forward towards the integration of DNA-based materials into nanoelectronic and sensor devices.
Topics: DNA; Nanostructures; Nanotechnology
PubMed: 33801952
DOI: 10.3390/molecules26061502 -
International Journal of Clinical... 2023Endometriosis, which is a common disease affecting approximately 10% of women of reproductive age, usually causes dysmenorrhea and infertility, thus seriously harming...
OBJECTIVE
Endometriosis, which is a common disease affecting approximately 10% of women of reproductive age, usually causes dysmenorrhea and infertility, thus seriously harming the patients' physical and mental health. However, there is a mean delay of 6.7 years between the onset of the symptoms and the surgical diagnosis of endometriosis. There is an increasing amount of evidence that suggests that epigenetic aberrations, including deoxyribonucleic acid (DNA) methylation, play a definite role in the pathogenesis of endometriosis. This study aimed to explore the noninvasive or minimally invasive biomarkers of this disease.
MATERIALS AND METHODS
Six patients with surgically confirmed ovarian endometriosis and six patients who received IUD implantation for contraception without endometriosis were recruited in the East Hospital of Tongji University in 2018. The genome methylation profiling of the eutopic and ectopic endometrium of ovarian endometriosis patients and normal endometrial specimens from healthy women was determined using a methylation microarray test. The test screened methylation-differentiated 5'-C-phosphate-G-3' (CpG) sites and then located the target genes affected by these sites following sequence alignment. Then, an additional 22 patients and 26 healthy controls were enrolled to further verify the difference in the selected genes between endometriosis patients and healthy women. The differential DNA methylation of the selected genes was validated via direct bisulfite sequencing and analysis of their messenger ribonucleic acid (mRNA) levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR).
RESULTS
Fifteen differentially methylated CpG sites were found among the patients and healthy women, and five CpG sites were mapped to the introns of the human leukocyte antigen-C (HLA-C) gene; these were highly polymorphic between different HLA-C alleles and were HLA-C07 specific. The results indicated that the HLA-C07 carrier patients exhibited significantly higher DNA methylation levels at the intron VII of HLA-C compared to the HLA-C07 carrier healthy controls. High HLA-C07 mRNA levels were also observed using qRT-PCR with HLA-C07-specific primers, which indicated that the hypermethylation of CpG in intron VII might suppress a silencer that regulates HLA-C07 expressions.
CONCLUSION
Deoxyribonucleic acid hypermethylation in the intron VII of the HLA-C07 gene appears to regulate the expression of HLA-C07. The aberrant DNA methylation in this region was positively correlated with the occurrence of endometriosis.
Topics: Humans; Female; DNA Methylation; Endometriosis; Introns; HLA-C Antigens; RNA, Messenger; DNA
PubMed: 36974156
DOI: 10.1155/2023/2291156 -
Medicine Mar 2022To evaluate the performance of polymerase chain reaction (PCR)-free whole genome sequencing (WGS) for clinical diagnosis, and thereby revealing how experimental...
To evaluate the performance of polymerase chain reaction (PCR)-free whole genome sequencing (WGS) for clinical diagnosis, and thereby revealing how experimental parameters affect variant detection.Five NA12878 samples were sequenced using MGISEQ-2000. NA12878 samples underwent WGS with differing deoxyribonucleic acid (DNA) input and library preparation protocol (PCR-based vs PCR-free protocols for library preparation). The depth of coverage and genotype quality of each sample were compared. The performance of each sample was measured for sensitivity, coverage of depth and breadth of coverage of disease-related genes, and copy number variants. We also developed a systematic WGS pipeline (PCR-free) for the analysis of 11 clinical cases.In general, NA12878-2 (PCR-free WGS) showed better depth of coverage and genotype quality distribution than NA12878-1 (PCR-based WGS). With a mean depth of ∼40×, the sensitivity of homozygous and heterozygous single nucleotide polymorphisms (SNPs) of NA12878-2 showed higher sensitivity (>99.77% and >99.82%) than NA12878-1, and positive predictive value exceeded 99.98% and 99.07%. The sensitivity and positive predictive value of homozygous and heterozygous indels for NA12878-2 (PCR-free WGS) showed great improvement than NA128878-1. The breadths of coverage for disease-related genes and copy number variants are slightly better for samples with PCR-free library preparation protocol than the sample with PCR-based library preparation protocol. DNA input also influences the performance of variant detection in samples with PCR-free WGS. All the 19 previously confirmed variants in 11 clinical cases were successfully detected by our WGS pipeline (PCR free).Different experimental parameters may affect variant detection for clinical WGS. Clinical scientists should know the range of sensitivity of variants for different methods of WGS, which would be useful when interpreting and delivering clinical reports.
Topics: DNA; DNA Copy Number Variations; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Whole Genome Sequencing
PubMed: 35451387
DOI: 10.1097/MD.0000000000028972