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Cell-Free Mitochondrial DNA as a Potential Biomarker for Astronauts' Health.

ABSTRACT: Background Space travel-associated stressors such as microgravity or radiation exposure have been reported in astronauts after short- and long-duration missions aboard the International Space Station. Despite risk mitigation strategies, adverse health effects remain a concern. Thus, there is a need to develop new diagnostic tools to facilitate early detection of physiological stress. Methods and Results We measured the levels of circulating cell-free mitochondrial DNA in blood plasma of 14 astronauts 10 days before launch, the day of landing, and 3 days after return. Our results revealed a significant increase of cell-free mitochondrial DNA in the plasma on the day of landing and 3 days after return with vast ~2 to 355-fold interastronaut variability. In addition, gene expression analysis of peripheral blood mononuclear cells revealed a significant increase in markers of inflammation, oxidative stress, and DNA damage. Conclusions Our study suggests that cell-free mitochondrial DNA abundance might be a biomarker of stress or immune response related to microgravity, radiation, and other environmental factors during space flight.

SUBMITTER: Bisserier M

PROVIDER: S-EPMC8751818 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Cell-Free Mitochondrial DNA in the CSF: A Potential Prognostic Biomarker of Anti-NMDAR Encephalitis.

Project description:Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune inflammatory brain disease that can develop a variety of neuropsychiatric presentations. However, the underlying nature of its inflammatory neuronal injury remains unclear. Mitochondrial DNA (mtDNA) is recently regarded as a damage-associated molecular pattern molecule (DAMP) that can initiate an inflammatory response. In the presenting study, we aimed to evaluate the levels of cell-free mtDNA in cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis and to determine a potential role of cell-free mtDNA in the prognosis of anti-NMDAR encephalitis. A total of 33 patients with NMDAR encephalitis and 17 patients with other non-inflammatory disorders as controls were included in this study. The CSF levels of cell-free mtDNA were measured by quantitative polymerase chain reaction (qPCR). Cytokines including interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-?) were measured by ELISA. The modified Rankin scale (mRS) score was evaluated for neurologic disabilities. Our data showed that the CSF levels of cell-free mtDNA and inflammation-associated cytokines were significantly higher in the patients with anti-NMDAR encephalitis compared with those in controls. Positive correlations were detected between the CSF levels of cell-free mtDNA and mRS scores of patients with anti-NMDAR encephalitis at both their admission and 6-month follow up. These findings suggest that the CSF level of cell-free mtDNA reflects the underlying neuroinflammatory process in patients with anti-NMDAR encephalitis and correlates with their clinical mRS scores. Therefore, cell-free mtDNA may be a potential prognostic biomarker for anti-NMDAR encephalitis.

| S-EPMC6375341 | biostudies-literature

Plasma cell-free DNA: a potential biomarker for early prediction of severe dengue.

Project description:BACKGROUND:Considerable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators, among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase. METHODS:This was a hospital-based prospective cohort study conducted in Vietnam. All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters (including progression to SD) until discharged. Plasma samples collected during acute phase (6-48 h before defervescence) were used to estimate the level of cfDNA. RESULTS:Of the 61 dengue patients, SD patients (n?=?8) developed shock syndrome in 4.8 days (95% CI 3.7-5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p?=?0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of?>?36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55-0.88; p?=?0.0493). CONCLUSIONS:Taken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD.

| S-EPMC6419393 | biostudies-literature

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

Project description: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-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating 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 identified 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.

| S-EPMC6076378 | biostudies-other

Cell-Free Circulating Mitochondrial DNA: A Potential Blood-Based Marker for Atrial Fibrillation.

Project description:Atrial fibrillation (AF), the most common, progressive tachyarrhythmia is associated with serious complications, such as stroke and heart failure. Early recognition of AF, essential to prevent disease progression and therapy failure, is hampered by the lack of accurate diagnostic serum biomarkers to identify the AF stage. As we previously showed mitochondrial dysfunction to drive experimental and human AF, we evaluated whether cell-free circulating mitochondrial DNA (cfc-mtDNA) represents a potential serum marker. Therefore, the levels of two mtDNA genes, COX3 and ND1, were measured in 84 control patients (C), 59 patients undergoing cardiac surgery without a history of AF (SR), 100 paroxysmal (PAF), 116 persistent (PeAF), and 20 longstanding-persistent (LS-PeAF) AF patients undergoing either cardiac surgery or AF treatment (electrical cardioversion or pulmonary vein isolation). Cfc-mtDNA levels were significantly increased in PAF patients undergoing AF treatment, especially in males and patients with AF recurrence after AF treatment. In PeAF and LS-PeAF, cfc-mtDNA levels gradually decreased. Importantly, cfc-mtDNA in serum may originate from cardiomyocytes, as in vitro tachypaced cardiomyocytes release mtDNA in the medium. The findings suggest that cfc-mtDNA is associated with AF stage, especially in males, and with patients at risk for AF recurrence after treatment.

| S-EPMC7290331 | biostudies-literature

Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer.

Project description:BackgroundNon-small cell lung cancer (NSCLC) is leading cause of cancer related death and the survival rate for patients with NSCLC remain poor so early diagnosis of NSCLC represents the best opportunity for cure. Cell-free DNA (cf-DNA) is extracellular nucleic acids found in cell-free plasma/serum of humans, given the recent approval of a liquid biopsy in lung cancer, the use of circulating tumor DNA as a novel non-invasive diagnostic and prognostic biomarker is promising.ObjectivesStudying whether the concentrations of circulating Cell Free DNA in serum can be used as a diagnostic and prognostic biomarker for NSCLC patients.MethodThis study was carried out on 140 subjects included 60 patients with non small cell lung cancer,40 patients with Chronic Obstructive Pulmonary Disease (COPD) and 40 healthy controls. Quantitative analysis of serum circulating cf-DNA was done b y AlU-based quantitative real time PCR. Serum level of CEA was measured by ELISA.ResultsNSCLC patients demonstrated significantly higher values of each of ALU 215, ALU 247, and DNA integrity than both COPD patients and controls. On ROC curve analysis, the total accuracy of ALU 247, ALU 115, DNA integrity (92.1%, 83.6%, 56.4%) at cutoff points (325, 565 & 0.48) respectively. On combining both DNA integrity and CEA, improved sensitivity to 93.3% was noted. For NSCLC patients, ALU 115 & ALU 247 increased significantly with more advanced stage and highest level was noticed in metastatic patients. Regarding survival there was better overall survival among patients with low DNA integrity.ConclusionSerum cf-DNA concentrations and integrity index may be valuable tool in early diagnosis of NSCLC and prediction of prognosis of those patients.

| S-EPMC6031238 | biostudies-literature

Cell-free DNA as a biomarker of aging.

Project description:Cell-free DNA (cfDNA) is present in the circulating plasma and other body fluids and is known to originate mainly from apoptotic cells. Here, we provide the first in vivo evidence of global and local chromatin changes in human aging by analyzing cfDNA from the blood of individuals of different age groups. Our results show that nucleosome signals inferred from cfDNA are consistent with the redistribution of heterochromatin observed in cellular senescence and aging in other model systems. In addition, we detected a relative cfDNA loss at several genomic locations, such as transcription start and termination sites, 5'UTR of L1HS retrotransposons and dimeric AluY elements with age. Our results also revealed age and deteriorating health status correlate with increased enrichment of signals from cells in different tissues. In conclusion, our results show that the sequencing of circulating cfDNA from human blood plasma can be used as a noninvasive methodology to study age-associated changes to the epigenome in vivo.

| S-EPMC6351822 | biostudies-literature

Biomarker study using cell free DNA in patients with colorectal cancer

Project description:Primary outcome(s): To assess the association between the presence of some somatic mutations and expression levels of cytokines in plasma and efficacy of some anti-tumor drugs.

| 2633274 | ecrin-mdr-crc

Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Systematic Review.

Project description:Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

| S-EPMC8005001 | biostudies-literature

Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review.

Project description:Kidney transplantation (KTx) is the best treatment method for end-stage kidney disease. KTx improves the patient's quality of life and prolongs their survival time; however, not all patients benefit fully from the transplantation procedure. For some patients, a problem is the premature loss of graft function due to immunological or non-immunological factors. Circulating cell-free DNA (cfDNA) is degraded deoxyribonucleic acid fragments that are released into the blood and other body fluids. Donor-derived cell-free DNA (dd-cfDNA) is cfDNA that is exogenous to the patient and comes from a transplanted organ. As opposed to an invasive biopsy, dd-cfDNA can be detected by a non-invasive analysis of a sample. The increase in dd-cfDNA concentration occurs even before the creatinine level starts rising, which may enable early diagnosis of transplant injury and adequate treatment to avoid premature graft loss. In this paper, we summarise the latest promising results related to cfDNA in transplant patients.

| S-EPMC7827757 | biostudies-literature

Cell-free mitochondrial DNA in progressive multiple sclerosis.

Project description:Recent studies have linked cell-free mitochondrial DNA (ccf-mtDNA) to neurodegeneration in both Alzheimer's and Parkinson's disease, raising the possibility that the same phenomenon could be seen in other diseases which manifest a neurodegenerative component. Here, we assessed the role of circulating cell-free mitochondrial DNA (ccf-mtDNA) in end-stage progressive multiple sclerosis (PMS), where neurodegeneration is evident, contrasting both ventricular cerebral spinal fluid ccf-mtDNA abundance and integrity between PMS cases and controls, and correlating ccf-mtDNA levels to known protein markers of neurodegeneration and PMS. Our data indicate that reduced ccf-mtDNA is a component of PMS, concluding that it may indeed be a hallmark of broader neurodegeneration.

| S-EPMC6509276 | biostudies-literature

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