Mitochondrial DNA as DAMP in critical conditions

Григорьев, Е. В.; Салахов, Р. Р.; Голубенко, М. В.; Понасенко, А. В.; Шукевич, Д. Л.; Матвеева, В. Г.; Радивилко, А. С.; Цепокина, А. В.; Великанова, Е. А.; Корнелюк, Р. А.; Ивкин, А. А.

doi:10.20538/1682-0363-2019-3-134-143

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…TLR9 signaling may be triggered by mtDNA, resulting in systemic inflammation, which includes inflammatory mediator overproduction and leukocyte activation [157]. To treat people infected with mutant mtDNA, CRISPR-Cas9 technology can be utilized to delete specific sequences of mutated DNA [158]. The Ccl2 gene product regulates the trafficking of inflammatory monocytes/macrophages, basophils and T lymphocytes in response to inflammatory signals such as TNF-and IL-1 [159].…”

Section: Crispr-cas9mentioning

confidence: 99%

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods

et al. 2023

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Sepsis is one of the deadliest disorders in the new century due to specific limitations in early and differential diagnosis. Moreover, antimicrobial resistance (AMR) is becoming the dominant threat to human health globally. The only way to encounter the spread and emergence of AMR is through the active detection and identification of the pathogen along with the quantification of resistance. For better management of such disease, there is an essential requirement to approach many suitable diagnostic techniques for the proper administration of antibiotics and elimination of these infectious diseases. The current method employed for the diagnosis of sepsis relies on the conventional culture of blood suspected infection. However, this method is more time consuming and generates results that are false negative in the case of antibiotic pretreated samples as well as slow-growing microbes. In comparison to the conventional method, modern methods are capable of analyzing blood samples, obtaining accurate results from the suspicious patient of sepsis, and giving all the necessary information to identify the pathogens as well as AMR in a short period. The present review is intended to highlight the culture shift from conventional to modern and advanced technologies including their limitations for the proper and prompt diagnosing of bloodstream infections and AMR detection.

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Section: Crispr-cas9mentioning

confidence: 99%

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods

et al. 2023

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The features of developing rat autoimmune pathology with mitochondrial dysfunction

Skupnevskiy¹,

Pukhaeva²,

Badtiev³

et al. 2023

Russian Journal of Infection and Immunity

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The central role of the mitochondria in energy supply and cell death determines highlight these organelles as one of the promising objects for investigating pathogenesis of immune-mediated inflammatory disorders. The aim: to study features of pathogenesis in rat adjuvant-induced autoimmune pathology separately and in combination with mitochondrial disorders. Materials and methods: Wistar rats were divided into groups of negative control (solvent), positive control (single subcutaneous injection of complete Freund's adjuvant (CAF) at dose of 0.1 ml/200 g body weight), experimental (CAF 0.1 ml/ 200 g body weight and 5 weeks later with cuprizone 0.2% per feed weight). At the end of experiment (7 weeks), animals were tested in the "open field" model, euthanized, and biomaterial was collected to measure the relative mass coefficients of internal organs, hematological and histological studies. We calculated the mean, standard error of the mean; comparison of hypotheses was carried out by paired Student's t-test. Results: in case of impaired immunological tolerance there was detected reduced rat body weight gain during the study period (negative control +74.7 g, positive control +10.3 g) along with modelled mitochondrial dysfunction, a general decrease in weight by 6.7 g was noted. The magnitude of mass coefficients indicate a relative reduction in mass of liver, kidneys, spleen and thymus in experimental animals. The leukocyte counts (x109/L) are as follows: negative control 8.680.37, positive control 10.981.03 (p0.05), experimental group 12.280.63 (p0.001). No significant changes were found in the leukocyte formula and the red cell lineage. During modelled autoimmune pathology, platelet count increased by 22.5% (p0.05), whereas after cuprizone was administered it decreased by 6.3% (relative to the negative control). Mitochondrial dysfunction caused an abrupt decrease in motor activity in rats: the number of crossed sectors in positive control animals was 55.506.91, experimental group 44.503.60 (inter-group comparison, p0.001). Positive control: enlarged lymphatic nodules were found in the spleen, germinal center clarification, wall thickening of the pulpal and central arteries; single foci of hemorrhages in the red pulp. Experimental group: atrophy of lymphoid follicles of varying severity (relative to the groups of negative and positive controls), numerous foci of hemorrhages with hemosiderosis in the red pulp. Conclusion: mitochondrial dysfunction is accompanied by augmented pathogenetic signs of autoimmune pathology, which can serve as one of the keys to understanding the mechanisms of human autoimmunity.

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Inflammatory markers and organ dysfunction in patients with severe influenza A (H1N1) virus-associated pneumonia

Malyarchikov

Шаповалов

Morozova

et al. 2022

Fundamentalʹnaâ i kliničeskaâ medicina

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Aim. To assess inflammatory markers and organ dysfunction in patients with severe influenza A (H1N1) virus-associated pneumonia.Materials and Methods. The study included 50 patients (median age 47 (38-62) years, 24 males and 26 females) with severe influenza A (H1N1) virus-associated pneumonia. We analysed the clinicopathological data as well as complete blood count and biochemical profile. Organ dysfunction was assessed using SOFA and qSOFA scales.Results. The prevalence of multiple organ dysfunction syndrome in patients with severe influenza A (H1N1) virus-associated pneumonia was 46% (23/50 patients). Patients frequently suffered from insufficient oxygenation, impaired coagulation, altered haemodynamics, and central nervous system dysfunction. Out of 23 patients with multiple organ dysfunction syndrome, 10 (43.5%) suffered from reduced oxygenation and excessive coagulation, while 6 (26.0%) had all mentioned syndromes combined. Thrombocytopenia was detected as early as at day 1-2 of the disease and was further accompanied by an increase in the erythrocyte sedimentation rate and white blood cell count from day 2 to day 8. An increase in acute-phase proteins (C-reactive protein and fibrinogen) was noted at the day 5-6 of the disease.Conclusion. In patients with severe influenza A (H1N1) virus-associated pneumonia, an early systemic inflammatory response evolves into an uncontrolled multiple organ dysfunction syndrome by day 7-8 of infection.

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Mitochondrial DNA as DAMP in critical conditions

Cited by 3 publications

References 53 publications

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods

The features of developing rat autoimmune pathology with mitochondrial dysfunction

Inflammatory markers and organ dysfunction in patients with severe influenza A (H1N1) virus-associated pneumonia

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