scholarly journals Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19

2021 ◽  
Vol 11 ◽  
Author(s):  
José J. Valdés-Aguayo ◽  
Idalia Garza-Veloz ◽  
José R. Vargas-Rodríguez ◽  
María C. Martinez-Vazquez ◽  
Lorena Avila-Carrasco ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Peripheral Blood ◽  
Mitochondrial Gene ◽  
Mt Dna ◽  
Qrt Pcr ◽  
Potential Biomarker ◽  
Inflammatory State ◽  
Patient’S Outcome ◽  
Severity Of The Disease ◽  
Early Predictor

IntroductionDuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient’s outcome.MethodsA total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene.ResultsThere were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/μl ± 0.30) and controls (3.3 ng/μl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/μl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/μl) were also observed (p = 0.037).ConclusionHigh levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.

scholarly journals PERIPHERAL BLOOD MITOCHONDRIAL DNA ALTERATION DURING SYSTEMIC LUPUS NEPHRITIS

2021 ◽  
Vol 10 (19) ◽  
pp. 416-421
Author(s):  
Ruchi Upadhyay ◽  
Ratika Srivastava
Keyword(s):  
Mitochondrial Dna ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Normal Subjects ◽  
Mitochondrial Genes ◽  
Systemic Lupus ◽  
Mt Dna ◽  
Mitochondrial Dna Copy Number ◽  
Genes Encoding

The investigation of mitochondrial DNA (Mt-DNA) alterations could impart light on the involvement of mitochondria in the pathophysiology of Systemic Lupus Erythematosus. The purpose of this study is to examine the peripheral blood mitochondrial DNA copy number variation in Lupus Nephritis patients and also to find out it’s correlation with amount of protein present in urine. The significant correlation could aid in the inspection of mitochondrial involvement, particularly in Lupus Nephritis. Two mitochondrial genes encoding MT-CYT and MT-TL1 were measured quantitatively by qRT-PCR in whole blood of 17 SLE patients and 15 healthy subjects with similar gender (female: male ratio) and age group. The amount of mitochondrial genes MT-CYT and MT-TL1 was 1.69 and 1.26 fold higher respectively in patients. The significantly higher amount of protein detected in lupus nephritis patients (129.4±116.4 mg/dl) in comparison to normal subjects (25.3 ±10.7 mg/dl). No significant correlation was established between Mt-DNA quantity and proteinuria. Alteration in mitochondrial genes reflects the possibilities of altered mitophagy or mitochondrial biosynthesis during SLE. These findings are required to be further validated by studying mitophagy and biogenesis during SLE in details.

scholarly journals Assessment of cell free mitochondrial DNA as a biomarker of disease severity in different viral infections

2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Zain Ali ◽  
Shahid Waseem ◽  
Riffat Aysha Anis ◽  
Mariam Anees
Keyword(s):  
Mitochondrial Dna ◽  
Viral Load ◽  
Disease Severity ◽  
Original Work ◽  
Viral Infections ◽  
Mt Dna ◽  
Creative Commons ◽  
Dna And Rna ◽  
Potential Biomarker ◽  
Open Access Article

Objective: Cell Free mitochondrial DNA (CF mt-DNA) has emerged as a novel biomarker to investigate disease pathophysiology of different infections. The present study was designed to elucidate the association between CF mt-DNA, IL-6 and viral load in HIV, HBV and HCV infections and predict its role as a potential biomarker to assess the disease severity in viral infections. Methods: Total 120 blood samples were collected from January 2018 to December 2018 of HIV, HBV and HCV patients and healthy controls (30 samples in each group). DNA and RNA were extracted from the serum to determine the levels of CF mt-DNA and viral load, respectively. IL-6 from the serum of infected individuals was quantified with ELISA. Results: HCV patients showed the highest levels of CF mt-DNA, IL-6 and viral load, followed by HBV and HIV. Significant correlation was found between CF mt-DNA and IL-6 among the HBV patients (p=0.017). However, no significant correlation of CF mt-DNA was observed with IL-6 in HIV and HCV or with the viral load in any of the three infections. Conclusion: Elevated CF mt-DNA indicates its role in severity of viral infections. Independence of CF mt-DNA expression from viral load and IL-6 in case of HIV and HCV suggests involvement of other inflammatory pathways regulating CF mt-DNA elevation. doi: https://doi.org/10.12669/pjms.36.5.2476 How to cite this:Ali Z, Waseem S, Anis RA, Anees M. Assessment of cell free mitochondrial DNA as a biomarker of disease severity in different viral infections. Pak J Med Sci. 2020;36(5):---------. doi: https://doi.org/10.12669/pjms.36.5.2476 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 928
Author(s):  
José J. Valdés-Aguayo ◽  
Idalia Garza-Veloz ◽  
José I. Badillo-Almaráz ◽  
Sofia Bernal-Silva ◽  
Maria C. Martínez-Vázquez ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Viral Genome ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Defense System ◽  
Mt Dna ◽  
Double Membrane ◽  
Cell Defense ◽  
Inflammatory State ◽  
Potential Area

Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion’s membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.

P–517 The relationship between mitochondrial gene CYB (MT-CYB) single nucleotide polymorphisms and male infertility

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Jawish ◽  
F W Dahadhah ◽  
M Ei. Hammadeh ◽  
H Amor
Keyword(s):  
Mitochondrial Dna ◽  
Single Nucleotide Polymorphisms ◽  
Male Infertility ◽  
Male Fertility ◽  
Mitochondrial Gene ◽  
Nucleotide Polymorphisms ◽  
Control Groups ◽  
Mt Dna ◽  
Single Nucleotide ◽  
Frequency Test

Abstract Study question Do single nucleotide polymorphisms of the mitochondrial gene CYB (MT-CYB) affect male fertility? Summary answer there was a significant association between male fertility and rs527236194, rs28357373, and rs41504845 single nucleotide polymorphisms of the mitochondrial gene CYB (MT-CYB). What is known already Male infertility can be occurred as a result of various factors. However, genetic factors are detected in 15% of male infertility cases and can be classified into two groups: chromosomal abnormalities and single gene mutations. Sperm mitochondrial DNA alterations may have serious effects on spermatogenesis, sperm motility and the ability of sperm to fertilize the oocyte. Mutations of the MT-CYB gene might lead to various disorders and deficiencies specially in complex III which might interrupt in the ATP production process. Study design, size, duration: 111 semen samples were included in this prospectively designed study which carried out between 2017 and August 2019. Participants/materials, setting, methods: This study carried out at the Department of Obstetrics and Gynecology at Saarland University, Germany. Samples were divided into 67 subfertile “cases” and 44 fertile “control” groups. After preparation of semen samples by density gradient centrifugation, nuclear and mitochondrial DNA (MT-DNA) was extracted using QIAamp DNA Mini Kit from QIAGEN. Thereafter, the MT-DNA was amplified using REPLI-g Mitochondrial DNA Kit from QIAGEN, followed by PCR and Sanger sequencing steps. Main results and the role of chance A total of 13 single nucleotide polymorphisms (SNPs) in the MT-CYB gene in each of the case and control groups were detected. Eight SNPs were non-synonymous variants including: rs2853508, rs28357685, rs41518645, rs2853507, rs28357376, rs35070048, rs2853506, and rs28660155 and five SNPs were synonymous variants: rs527236194, rs28357373, rs28357369, rs41504845, and rs2854124.Among these SNPs, three of them showed a significant difference in the genotype’s frequency test between sub-fertile and fertile groups: rs527236194 (T15784C; P = 0.0005), rs28357373 (T15629C; P = 0.0439), and rs41504845 (C15833T; P = 0.0038). For the allele’s frequency test, two SNPs were significant: rs527236194 (T15784C; P = 0.0014) and rs41504845 (C15833T; P = 0.0147). Limitations, reasons for caution The study population size Wider implications of the findings: A larger prospective study will be required to confirm the associations between these mitochondrial gene polymorphisms in MT-CYB (rs527236194, rs28357373, rs41504845) and male infertility and to clarify the definite effect of the mitochondrial genetic variations on male infertility. Trial registration number Not applicable

Screening for differentially expressed circRNA between Kashin–Beck disease and osteoarthritis patients based on circRNA chips

2019 ◽  
Author(s):  
Ying Wang ◽  
Cuiyan Wu ◽  
Yanan Zhang ◽  
Yimin Yang ◽  
Zhiwei Ren ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Peripheral Blood ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Differentially Expressed ◽  
Joint Disease ◽  
Pcr Analysis ◽  
Mirna Regulation ◽  
Qrt Pcr ◽  
Potential Biomarker

Abstract Objective: The purpose of this research was to explore differentially expressed circRNA between OA and KBD and the potential differential diagnosis biomarkers.Methods: Total RNA was extracted from 5 pairs of KBD and OA knee joint cartilage specimens, and the expression of circRNAs was analyzed by Chip Scanning Analysis. The microarray data was verified by quantitative polymerase chain reaction (qRT-PCR) analysis. GO enrichment analysis and KEGG pathway were used to predict the functions of the differentially expressed circRNAs. A circRNA-miRNA network was constructed to predict targeting microRNAs of differentially expressed circRNA genes. On the basis of microarray, we expanded the sample size, peripheral blood samples from 25 KBD patients and 25 OA patients (five pairs of patients for chondrocyte microarray study included) were collected and qRT-PCR was performed for hsa_circRNA_0020014 verification. Diagnostic value was evaluated by the area under the receiver operator characteristic (ROC) curve.Results: A total of 1627 circRNAs were differentially expressed between OA and KBD (P<0.05; 0.5<fold change>2), 1328 were up-regulated and 299 were down-regulated among them. Five differentially expressed genes associated with bone and joint disease were chosen for further qRT-PCR validation. After obtaining the parental genes of them, functional annotations were performed on the top ten enrichment GO items and KEGG pathways. The difference in expression profile of hsa_circRNA_0020014 was confirmed by qRT-PCR at articular cartilage level, and its circRNA-miRNA regulation network was set up. The ROC curve demonstrated that hsa_circ_0020014_CBC1 in peripheral blood could distinguish patients with KBD and OA (area under the curve: 0.6415, P< 0.01). The hsa_circ_0020014_CBC1 may be a potential biomarker for differential diagnosis between KBD and OA patientsConclusion: Our results suggested that the expression profiles of circRNA were significantly different between OA and KBD. hsa_circRNA_0020014 is a potential biomarker for the differential diagnosis between these two diseases.

scholarly journals Changes in circulating cell-free nuclear DNA and mitochondrial DNA of patients with adolescent idiopathic scoliosis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiong Li ◽  
Longjie Wang ◽  
Guanteng Yang ◽  
Yunjia Wang ◽  
Chaofeng Guo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Sensitivity And Specificity ◽  
Dna Analysis ◽  
Nuclear Dna ◽  
Predictive Accuracy ◽  
Lower Sensitivity ◽  
Mt Dna ◽  
Potential Biomarker

Abstract Background Adolescent idiopathic scoliosis (AIS) which characterized by complex three-dimensional deformity of spine has been difficult to cure because of the unknown etiopathology and uncertainty of progression. Nowadays, circulating cell-free (ccf) DNA was found to be a potential biomarker for several benign and malignant diseases. However, whether ccf DNA can be a biomarker for AIS has not been reported yet. In this study, we investigate the circulating cell-free nuclear DNA (ccf n-DNA) and mitochondrial DNA (ccf mt-DNA) concentrations in the plasma of patients with AIS and controls (CT), and the changed plasma ccf n-DNA and ccf mt-DNA levels and their association with clinical parameters were assessed. Methods The plasma of peripheral blood from 69 AIS patients and 21 age-matched CT was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between the ccf n-DNA and ccf mt-DNA levels and clinical characteristics were conducted. Receiver operator curves (ROC) were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics. Results The plasma ccf n-DNA levels of both GAPDH and ACTB were significantly decreased in AIS patients compared with those in controls, while the plasma ccf mt-DNA levels did not changed. According to sex-related analyses, the ccf n-DNA levels in male CT-M was higher than that in female CT and male AIS, but the ccf n-DNA levels in female AIS was not significantly changed when compared with male AIS or female CT. However, the concentration of ccf mt-DNA in female AIS increased significantly when compared with male AIS. Surprisingly, Lenke type-related analyses suggested that Lenke type 1 patients had lower ccf n-DNA levels, whereas Lenke type 5 patients had higher ccf mt-DNA levels compared with those of controls. However, a lower sensitivity and specificity of AIS predicted by ccf n-DNA or ccf mt-DNA levels was observed, whether in total, by sex, or by Lenke type. Conclusion Although with no/little predictive accuracy of AIS/progressed AIS by ccf DNA levels, significantly changed plasma ccf DNA levels were observed in AIS patients compared with those in controls.

scholarly journals Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yi Wang ◽  
Guogang Dai ◽  
Ling Jiang ◽  
Shichuan Liao ◽  
Jiao Xia
Keyword(s):  
Functional Analysis ◽  
Network Analysis ◽  
Peripheral Blood ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Toll Like Receptor ◽  
Qrt Pcr ◽  
Transcriptomic Signature ◽  
Transcriptional Changes ◽  
Key Genes

Abstract Background Although the pathology of sciatica has been studied extensively, the transcriptional changes in the peripheral blood caused by sciatica have not been characterized. This study aimed to characterize the peripheral blood transcriptomic signature for sciatica. Methods We used a microarray to identify differentially expressed genes in the peripheral blood of patients with sciatica compared with that of healthy controls, performed a functional analysis to reveal the peripheral blood transcriptomic signature for sciatica, and conducted a network analysis to identify key genes that contribute to the observed transcriptional changes. The expression levels of these key genes were assessed by qRT-PCR. Results We found that 153 genes were differentially expressed in the peripheral blood of patients with sciatica compared with that of healthy controls, and 131 and 22 of these were upregulated and downregulated, respectively. A functional analysis revealed that these differentially expressed genes (DEGs) were strongly enriched for the inflammatory response or immunity. The network analysis revealed that a group of genes, most of which are related to the inflammatory response, played a key role in the dysregulation of these DEGs. These key genes are Toll-like receptor 4, matrix metallopeptidase 9, myeloperoxidase, cathelicidin antimicrobial peptide, resistin and Toll-like receptor 5, and a qRT-PCR analysis validated the higher transcript levels of these key genes in the peripheral blood of patients with sciatica than in that of healthy controls. Conclusion We revealed inflammatory characteristics that serve as a peripheral blood transcriptomic signature for sciatica and identified genes that are essential for mRNA dysregulation in the peripheral blood of patients with sciatica.

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