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ACS Nano Sep 2023Multidrug resistance (MDR) is a major cause of chemotherapy failure in oncology, and gene therapy is an excellent measure to reverse MDR. However, conventional gene...
Multidrug resistance (MDR) is a major cause of chemotherapy failure in oncology, and gene therapy is an excellent measure to reverse MDR. However, conventional gene therapy only modulates the expression of MDR-associated proteins but hardly affects their existing function, thus limiting the efficiency of tumor treatment. Herein, we designed a photoactivated DNA nanodrug (MCD@TMPyP@DOX) to improve tumor chemosensitivity through the downregulation of MDR-related genes and mitochondria-targeted photodynamic therapy (PDT). The self-assembled DNA nanodrug encodes the mucin 1 (MUC1) aptamer and the cytochrome C (CytC) aptamer to facilitate its selective targeting to the mitochondria in tumor cells; the encoded P-gp DNAzyme can specifically cleave the substrate and silence MDR1 mRNA with the help of Mg cofactors. Under near-infrared (NIR) light irradiation, PDT generates reactive oxygen species (ROS) that precisely damage the mitochondria of tumor cells and break single-stranded DNA (ssDNA) to activate MCD@TMPyP@DOX self-disassembly for release of DOX and DNAzyme. We have demonstrated that this multifunctional DNA nanodrug has high drug delivery capacity and biosafety. It enables downregulation of P-gp expression while reducing the ATP on which P-gp pumps out drugs, improving the latency of gene therapy and synergistically reducing DOX efflux to sensitize tumor chemotherapy. We envision that this gene-modulating DNA nanodrug based on damaging mitochondria is expected to provide an important perspective for sensitizing tumor chemotherapy.
Topics: DNA, Catalytic; Drug Resistance, Neoplasm; DNA; DNA, Single-Stranded; Genetic Therapy; Mitochondria; Nanoparticles
PubMed: 37606317
DOI: 10.1021/acsnano.3c04002 -
Fa Yi Xue Za Zhi Oct 2023Skeleton and teeth are important biological samples. Due to their special structure and strong ability to resist degradation, they are ideal biological materials to... (Review)
Review
Skeleton and teeth are important biological samples. Due to their special structure and strong ability to resist degradation, they are ideal biological materials to retain DNA under natural condition. In many cases, such as historical figure identification, aged skeleton and teeth are usually the only biological samples. However, their DNA is in a state of trace, damage and degradation to different degrees, which requires special experimental treatment to achieve identification. This paper reviews the sample selection, DNA extraction, DNA enrichment and analysis approaches based on relevant research reports in recent years, aiming to promote the further development and improvement of the aged skeleton and teeth identification system.
Topics: Humans; Aged; Body Remains; DNA; Tooth; DNA Fingerprinting; Sequence Analysis, DNA
PubMed: 38006268
DOI: 10.12116/j.issn.1004-5619.2021.511209 -
Trends in Biotechnology Jul 2023Qian and Winfree constructed complex biochemical circuits with computation capability from scratch, demonstrating the programmability of biomolecules. One day,...
Qian and Winfree constructed complex biochemical circuits with computation capability from scratch, demonstrating the programmability of biomolecules. One day, programming molecular information processing may be just like how electronic machines are programmed today, with exciting applications in nanoscale science and biotechnology.
Topics: Information Technology; DNA; Biotechnology; Nanotechnology; Electronic Data Processing
PubMed: 37127492
DOI: 10.1016/j.tibtech.2023.04.005 -
International Immunopharmacology Apr 2024Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the...
OBJECTIVES
Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples.
METHODS
The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient.
RESULTS
The study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64-0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63-0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61-0.96, a balanced accuracy range of 0.46-0.94, and an AUC range of 0.46-0.94.
CONCLUSIONS
This study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.
Topics: Female; Humans; DNA Methylation; Bayes Theorem; Arthritis, Rheumatoid; Osteoarthritis; Biomarkers; DNA; Neoplasms; Antigens, Neoplasm; Antigens, CD
PubMed: 38508093
DOI: 10.1016/j.intimp.2024.111860 -
Cell Chemical Biology Aug 2023CRISPR-based editing has revolutionized genome engineering despite the observation that many DNA sequences remain challenging to target. Unproductive interactions formed...
CRISPR-based editing has revolutionized genome engineering despite the observation that many DNA sequences remain challenging to target. Unproductive interactions formed between the single guide RNA's (sgRNA) Cas9-binding scaffold domain and DNA-binding antisense domain are often responsible for such limited editing resolution. To bypass this limitation, we develop a functional SELEX (systematic evolution of ligands by exponential enrichment) approach, termed BLADE (binding and ligand activated directed evolution), to identify numerous, diverse sgRNA variants that bind Streptococcus pyogenes Cas9 and support DNA cleavage. These variants demonstrate surprising malleability in sgRNA sequence. We also observe that particular variants partner more effectively with specific DNA-binding antisense domains, yielding combinations with enhanced editing efficiencies at various target sites. Using molecular evolution, CRISPR-based systems could be created to efficiently edit even challenging DNA sequences making the genome more tractable to engineering. This selection approach will be valuable for generating sgRNAs with a range of useful activities.
Topics: CRISPR-Cas Systems; RNA, Guide, CRISPR-Cas Systems; RNA; DNA; Gene Editing
PubMed: 37390831
DOI: 10.1016/j.chembiol.2023.06.007 -
Science Advances Sep 2023Lattice-based constructs, often made by additive manufacturing, are attractive for many applications. Typically, such constructs are made from microscale or larger...
Lattice-based constructs, often made by additive manufacturing, are attractive for many applications. Typically, such constructs are made from microscale or larger elements; however, smaller nanoscale components can lead to more unusual properties, including greater strength, lighter weight, and unprecedented resiliencies. Here, solid and hollow nanoparticles (nanoframes and nanocages; frame size: ~15 nanometers) were assembled into colloidal crystals using DNA, and their mechanical strengths were studied. Nanosolid, nanocage, and nanoframe lattices with identical crystal symmetries exhibit markedly different specific stiffnesses and strengths. Unexpectedly, the nanoframe lattice is approximately six times stronger than the nanosolid lattice. Nanomechanical experiments, electron microscopy, and finite element analysis show that this property results from the buckling, densification, and size-dependent strain hardening of nanoframe lattices. Last, these unusual open architectures show that lattices with structural elements as small as 15 nanometers can retain a high degree of strength, and as such, they represent target components for making and exploring a variety of miniaturized devices.
Topics: DNA; Nanoparticles
PubMed: 37774024
DOI: 10.1126/sciadv.adj8103 -
Medical & Biological Engineering &... Mar 2024Glioblastoma multiforme (GBM) is one of the deadliest tumours. This study aimed to construct radiogenomic prognostic models of glioblastoma overall survival (OS) based...
Glioblastoma multiforme (GBM) is one of the deadliest tumours. This study aimed to construct radiogenomic prognostic models of glioblastoma overall survival (OS) based on magnetic resonance imaging (MRI) Gd-T1WI images and deoxyribonucleic acid (DNA) methylation-seq and to understand the related biological pathways. The ResNet3D-18 model was used to extract radiomic features, and Lasso-Cox regression analysis was utilized to establish the prognostic models. A nomogram was constructed by combining the radiogenomic features and clinicopathological variables. The DeLong test was performed to compare the area under the curve (AUC) of the models. We screened differentially expressed genes (DEGs) with original ribonucleic acid (RNA)-seq in risk stratification and used Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotations for functional enrichment analysis. For the 1-year OS models, the AUCs of the radiogenomic set, methylation set and deep learning set in the training cohort were 0.864, 0.804 and 0.787, and those in the validation cohort were 0.835, 0.768 and 0.651, respectively. The AUCs of the 0.5-, 1- and 2-year nomograms in the training cohort were 0.943, 0.861 and 0.871, and those in the validation cohort were 0.864, 0.885 and 0.805, respectively. A total of 245 DEGs were screened; functional enrichment analysis showed that these DEGs were associated with cell immunity. The survival risk-stratifying radiogenomic models for glioblastoma OS had high predictability and were associated with biological pathways related to cell immunity.
Topics: Humans; Glioblastoma; Brain Neoplasms; Prognosis; Magnetic Resonance Imaging; Methylation; Risk Assessment; DNA
PubMed: 38057447
DOI: 10.1007/s11517-023-02971-3 -
JNMA; Journal of the Nepal Medical... Aug 2023Cervical cancer is one of the leading causes of morbidity and mortality among women globally as well as in Nepal. It is attributable to persistent infection by high-risk...
Knowledge of Cervical Cancer Screening and Prevention by Human Papillomavirus Deoxyribonucleic Acid and Human Papillomavirus Vaccination among Women Attending a Tertiary Care Centre.
INTRODUCTION
Cervical cancer is one of the leading causes of morbidity and mortality among women globally as well as in Nepal. It is attributable to persistent infection by high-risk human papillomavirus, especially human papillomavirus-16 and human papillomavirus-18. The aim of this study was to find out the knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination among women attending a tertiary care centre.
METHODS
A descriptive cross-sectional study was conducted in patients attending the outpatient Department of Gynaecology in a tertiary care centre from 18 March to 30 April 2023. After calculating sample size and taking a convenience sampling a survey questionnaire on knowledge of Cervical Cancer Screening and Prevention by Human Papillomavirus Deoxyribonucleic Acid and Human Papillomavirus Vaccination was collected. The point estimate was calculated at a 95% confidence interval.
RESULTS
Among 508 women, 42 (8.25%) (5.86-10.64, 95% Confidence Interval) had knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination. According to the questionnaires with a total sample of 508, 164 (32.28%) know about cervical cancer, 15 (2.95%) know about HPV infection, 14 (2.76%) know about HPV infection causes cervical cancer, and 21 (4.13%) know about HPV transmitted through multiple sex partners.
CONCLUSIONS
The knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination among women is very low. This study recommends having a health education and awareness programme on it to increase knowledge.
KEYWORDS
cervical cancer; human papillomavirus; pap smear; sexual intercourse; vaccination.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Early Detection of Cancer; Cross-Sectional Studies; Tertiary Care Centers; Health Knowledge, Attitudes, Practice; Papillomaviridae; Papillomavirus Vaccines; Vaccination; DNA
PubMed: 38289809
DOI: 10.31729/jnma.8248 -
Organic Letters Jul 2023In this study, we revealed two distinct S-glycosyl transformations in a DNA-encoded library (DEL)-compatible environment. The first approach involves...
In this study, we revealed two distinct S-glycosyl transformations in a DNA-encoded library (DEL)-compatible environment. The first approach involves 2-chloro-1,3-dimethylimidazolidinium chloride (DMC)-mediated S-glycosylation, which is facilitated by the coupling of unprotected sugar units with the thiol residue of the DNA-linked compounds. However, this methodology falls short of the requirement for DEL construction due to its limited substrate scope. We further investigated a photoinduced DNA-compatible S-glycosyl transformation through a radical process. In this alternative approach, allyl sugar sulfones serve as sugar donors and are conjugated to DNA-linked compounds upon irradiation with green light. Encouragingly, this on-DNA glycosyl chemistry demonstrated excellent compatibility with functional groups presented in both sugar units and peptides, affording the desired DNA-linked glycosyl derivatives with good to excellent conversions. This pioneering DNA-compatible S-glycosyl transformation represents a valuable tool, facilitating the preparation of glycosyl DELs and offering avenues for the exploration of sugar-incorporated delivery systems.
Topics: Sugars; Peptides; Sulfhydryl Compounds; Glycosylation; DNA
PubMed: 37358352
DOI: 10.1021/acs.orglett.3c01799 -
ChemPlusChem Sep 2023Fold-change detection is widespread in sensory systems of various organisms. Dynamic DNA nanotechnology provides an important toolbox for reproducing structures and...
Fold-change detection is widespread in sensory systems of various organisms. Dynamic DNA nanotechnology provides an important toolbox for reproducing structures and responses of cellular circuits. In this work, we construct an enzyme-free nucleic acid circuit based on the incoherent feed-forward loop using toehold-mediated DNA strand displacement reactions and explore its dynamic behaviors. The mathematical model based on ordinary differential equations is used to evaluate the parameter regime required for fold-change detection. After selecting appropriate parameters, the constructed synthetic circuit exhibits approximate fold-change detection for multiple rounds of inputs with different initial concentrations. This work is anticipated to shed new light on the design of DNA dynamic circuits in the enzyme-free environment.
Topics: Nucleic Acids; DNA; Nanotechnology
PubMed: 37005227
DOI: 10.1002/cplu.202300083