scholarly journals Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

2007 ◽  
Vol 53 (9) ◽  
pp. 1609-1614 ◽  
Author(s):  
Xiao-Yan Zhong ◽  
Ines von Mühlenen ◽  
Ying Li ◽  
Anjeung Kang ◽  
Anurag Kumar Gupta ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Animal Experiments ◽  
Basic Research ◽  
Healthy Controls ◽  
Serum Samples ◽  
Cell Free Dna ◽  
Free Dna ◽  
New Evidence

Abstract Background: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). Methods: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharose™ bead adsorption of plasma and elution to isolate antibody-bound DNA. Results: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319–21 000) and in 26 RA patients 17 000 GE/mL plasma (2100–2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700–239 000) and from RA patients 222 000 GE/mL (21 000–2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received. Conclusions: These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.

scholarly journals Nuclear and Mitochondrial Circulating Cell-Free DNA Is Increased in Patients With Inflammatory Bowel Disease in Clinical Remission

2020 ◽  
Vol 7 ◽  
Author(s):  
Zuzana Vrablicova ◽  
Kristina Tomova ◽  
Lubomira Tothova ◽  
Janka Babickova ◽  
Barbora Gromova ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Nuclear Dna ◽  
Dnase Activity ◽  
Healthy Controls ◽  
Cell Free Dna ◽  
Free Dna ◽  
Inflammatory Bowel

Background: The role of cell-free DNA (cfDNA) in the pathogenesis of inflammatory bowel disease (IBD) has been recently suggested. The aim of this study was to analyze circulating cfDNA and deoxyribonuclease (DNase) activity in IBD patients in clinical remission.Materials and Methods: Plasma and serum were obtained from 72 patients with Crohn's disease and 28 patients with ulcerative colitis. Total cfDNA, nuclear DNA (ncDNA), mitochondrial DNA (mtDNA) and DNase activity were measured.Results: IBD patients showed higher levels of both ncDNA and mtDNA compared to healthy controls. Concentration of ncDNA was higher in males compared to females, including patients and healthy controls. However, unlike males higher amount of ncDNA was found in female IBD patients compared to healthy controls. DNase activity was significantly lower in male IBD patients compared with healthy controls. In addition, there was a negative correlation between DNase activity and ncDNA levels in male IBD patients.Conclusions: Herein we present increased amount of circulating ncDNA and mtDNA in IBD patients in clinical remission. Thus, unlike total cfDNA, circulating ncDNA and mtDNA might not represent the optimal biomarkers of disease activity. This is also the first report on sex difference in circulating ncDNA levels, possibly associated with lower DNase activity in males.

scholarly journals The role of cell-free DNA in fibrinolysis for intraventricular hemorrhage

2021 ◽  
pp. 1-8
Author(s):  
Fangke Xie ◽  
Qiang Tan ◽  
Anyong Yu ◽  
Peiwen Guo ◽  
Ling Wang ◽  
...  
Keyword(s):  
Intraventricular Hemorrhage ◽  
Ventricular Volume ◽  
Intraventricular Injection ◽  
Ventricular Dilation ◽  
Cell Free Dna ◽  
Astrocyte Proliferation ◽  
Free Dna ◽  
Intraventricular Fibrinolysis

OBJECTIVETissue plasminogen activator (tPA) fibrinolysis did not improve functional outcomes of patients with intraventricular hemorrhage (IVH), largely because of the unsatisfactory clot clearance. The presence of neutrophil extracellular traps (NETs) within the clot has been confirmed to impair tPA fibrinolysis, but the mechanism has been unclear. The authors hypothesized that cell-free DNA (cfDNA), the main framework of NETs, might be the important reason for the fibrinolysis resistance, and they validated the hypothesis, hoping to provide a new target to promote intraventricular fibrinolysis.METHODSFirst, cfDNA was detected in IVH clots by immunofluorescence staining in a rat model of IVH. Second, after blood (with or without exogenous cfDNA) intraventricular injection, IVH rats were given intraventricular infusion of 2 μl of saline, tPA, or tPA + DNase1 randomly. Then, the ventricular volume, animal behavior, and reactive astrocyte proliferation were assessed. Third, the IVH clots were collected for fibrinolysis assay in vitro. Finally, the effects of exogenous cfDNA in IVH were evaluated.RESULTSThe presence of cfDNA in clots was observed as early as 1 hour after IVH. Compared with the whole-blood model, blood + cfDNA caused more severe ventricular dilation (day 7: blood 32.47 ± 2.096 mm3 vs blood + DNA 40.09 ± 2.787 mm3, p < 0.05), increased fibrinolysis resistance to tPA (day 7: tPA + DNA 26.04 ± 1.318 mm3 vs tPA 22.15 ± 1.706 mm3, p < 0.05), and further deteriorated the functional defects in rats (blood vs blood + DNA, p < 0.05). Degradation of cfDNA by DNase1 further enhanced the fibrinolysis effects on relieving the ventricular dilation (day 7: tPA + DNase1 11.67 ± 2.023 mm3 vs tPA, p < 0.05), improving the functional outcome (tPA vs tPA + DNase1, p < 0.05) and reducing periventricular astrocyte proliferation.CONCLUSIONScfDNA impaired tPA fibrinolysis for IVH, and degradation of cfDNA may be a new target to improve this condition.

scholarly journals The Role of Natural Products in Rheumatoid Arthritis: Current Knowledge of Basic In Vitro and In Vivo Research

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 599
Author(s):  
Georgia-Eirini Deligiannidou ◽  
Vasiliki Gougoula ◽  
Eugenia Bezirtzoglou ◽  
Christos Kontogiorgis ◽  
Theodoros K. Constantinides
Keyword(s):  
Rheumatoid Arthritis ◽  
Natural Products ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Relevant Literature ◽  
Basic Research ◽  
Publication Date

Rheumatoid arthritis (RA) is an autoimmune disorder affecting a vast variety of the population. The onset of RA as well as the development of systematic immunization is affected by both genetic and environmental risk factors. This review aims to point out the role of natural products in the management of RA, focusing on the reports of basic research (in vitro and animal studies) emphasizing the antioxidant and anti-inflammatory properties considered in the field of RA. A systematic screening of the relevant literature was carried out on PubMed, Google Scholar, and Scopus with the following criteria: publication date, 2015–2020; language, English; study design, in vitro or animal models; and the investigation of one or several natural products in the context of RA, including, when available, the molecular mechanisms implicated. A total of 211 papers were initially obtained and screened. In vitro and animal studies referring to 20 natural products and 15 pure compounds were ultimately included in this review. The outcomes of this work provide an overview of the methods employed in basic research over the past five years, with emphasis on the limitations presented, while demonstrating the potential benefits of utilizing natural products in the management of RA as supported by in vitro and animal studies.

Emerging Role of Genomics and Cell-Free DNA in Breast Cancer

2019 ◽  
Vol 20 (8) ◽  
Author(s):  
Lorenzo Gerratana ◽  
Andrew A. Davis ◽  
Ami N. Shah ◽  
Chenyu Lin ◽  
Carla Corvaja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Free Dna ◽  
Free Dna

The role of donor-derived cell-free DNA in the detection of renal allograft injury

2021 ◽  
Vol 17 (1) ◽  
pp. 12-17
Author(s):  
Yang Zhou ◽  
Dongrui Cheng ◽  
Tingya Jiang
Keyword(s):  
Renal Allograft ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vida Ungerer ◽  
Abel J. Bronkhorst ◽  
Priscilla Van den Ackerveken ◽  
Marielle Herzog ◽  
Stefan Holdenrieder
Keyword(s):  
Cancer Cells ◽  
Histone Modifications ◽  
Chemical Properties ◽  
Basic Research ◽  
Live Cells ◽  
Cycle Phase ◽  
Cell Free Dna ◽  
Free Dna ◽  
High Resolution Analysis ◽  
Active Release

AbstractRecent advances in basic research have unveiled several strategies for improving the sensitivity and specificity of cell-free DNA (cfDNA) based assays, which is a prerequisite for broadening its clinical use. Included among these strategies is leveraging knowledge of both the biogenesis and physico-chemical properties of cfDNA towards the identification of better disease-defining features and optimization of methods. While good progress has been made on this front, much of cfDNA biology remains uncharted. Here, we correlated serial measurements of cfDNA size, concentration and nucleosome histone modifications with various cellular parameters, including cell growth rate, viability, apoptosis, necrosis, and cell cycle phase in three different cell lines. Collectively, the picture emerged that temporal changes in cfDNA levels are rather irregular and not the result of constitutive release from live cells. Instead, changes in cfDNA levels correlated with intermittent cell death events, wherein apoptosis contributed more to cfDNA release in non-cancer cells and necrosis more in cancer cells. Interestingly, the presence of a ~ 3 kbp cfDNA population, which is often deemed to originate from accidental cell lysis or active release, was found to originate from necrosis. High-resolution analysis of this cfDNA population revealed an underlying DNA laddering pattern consisting of several oligo-nucleosomes, identical to those generated by apoptosis. This suggests that necrosis may contribute significantly to the pool of mono-nucleosomal cfDNA fragments that are generally interrogated for cancer mutational profiling. Furthermore, since active steps are often taken to exclude longer oligo-nucleosomes from clinical biospecimens and subsequent assays this raises the question of whether important pathological information is lost.

scholarly journals Levels of Circulating TIMP-2 and MMP2-TIMP2 Complex Are Decreased in Squamous Cervical Carcinoma

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Talvensaari-Mattila Anne ◽  
Turpeenniemi-Hujanen Taina
Keyword(s):  
Cervical Carcinoma ◽  
Matrix Metalloproteinase 2 ◽  
Healthy Controls ◽  
Matrix Degradation ◽  
Serum Samples ◽  
Study Population ◽  
The Mean ◽  
Natural Tissue ◽  
Squamous Cervical Carcinoma

Background. The role of matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in matrix degradation and metastasis has been described in various tumors. Their action is inhibited by their natural tissue inhibitor molecules TIMP-1 and -2.Methods. The study population consisted of 12 squamous cervical carcinoma patients and 27 healthy volunteer control patients. MMP-9, MMP-2-TIMP-2 complex, TIMP-1, and TIMP-2 were analyzed from serum samples using enzyme-linked immunoassay (ELISA).Results. The mean levels of serum TIMP-2 and of MMP-2-TIMP-2 complex were higher in healthy controls compared to patients with a malignant tumor. Serum TIMP-2 values decreased significantly from healthy controls (median 323 g/l, range 305–342 g/l) to malignant (median 136 g/l, range 120–151 g/l) squamous cervical carcinoma patients . Also, serum proMMP2-TIMP2 complex values decreased from control patients to squamous cervical carcinoma patients .Conclusion. This paper shows that the levels of circulating TIMP-2 and that of MMP-2-TIMP-2 complex are lower in squamous cervical carcinoma patients than in healthy women.

scholarly journals Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Brian C.-H. Chiu ◽  
Chang Chen ◽  
Qiancheng You ◽  
Rudyard Chiu ◽  
Girish Venkataraman ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Non Invasive ◽  
Signature Genes ◽  
Non Hodgkin Lymphoma ◽  
Free Dna ◽  
Genome Wide ◽  
Circulating Cell Free Dna

AbstractThe 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.

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