Comparison of plasma mitochondrial DNA copy number in asymptomatic and symptomatic COVID-19 patients DOI Creative Commons
Shahrzad Shoraka, Seyed Reza Mohebbi, Seyed Masoud Hosseini

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 6, 2023

Introduction Since the beginning of COVID-19 pandemic, a wide clinical spectrum, from asymptomatic infection to mild or severe disease and death, have been reported in patients. Studies suggested several possible factors, which may affect outcome COVID-19. A pro-inflammatory state impaired antiviral response as major contributing factors Considering that mitochondria an important role regulating immune responses pathogens, signaling, cell it has received much attention SARS-CoV-2 infection. Recent studies demonstrated high levels cell-free mitochondrial DNA ( cf -mtDNA) are associated with increased risk intensive care unit (ICU) admission mortality. However, there few on -mtDNA infection, mainly focusing critically ill cases. In present study, we investigated copy number patients compared between symptomatic cases, assessed values. We also determined -nuclear -nDNA) transcription factor (TFAM) mRNA level studied groups. Materials methods Plasma buffy coat samples were collected 37 33 controls. Briefly, after total extraction, plasma -mtDNA, -nDNA numbers measured by absolute qPCR using standard curve method. Furthermore, RNA extraction cDNA synthesis, TFAM evaluated qPCR. Results The results showed statistically significantly higher than cases p value = 0.01). 0.00). There was no significant difference these two groups > 0.05). Also, good diagnostic potential subgroups. Conclusion is probably due its inflammation response. It can be promising candidate biomarker for diagnosis Further investigation will help understanding pathophysiology effective therapeutic strategies.

Language: Английский

Apoptotic cell death in disease—Current understanding of the NCCD 2023 DOI Open Access
Ilio Vitale, Federico Pietrocola, Emma Guilbaud

et al.

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(5), P. 1097 - 1154

Published: April 26, 2023

Language: Английский

Citations

211
COVID-19, Myocarditis and Pericarditis DOI Creative Commons
DeLisa Fairweather, Danielle J. Beetler, Damian N. Di Florio

et al.

Circulation Research, Journal Year: 2023, Volume and Issue: 132(10), P. 1302 - 1319

Published: May 11, 2023

Viral infections are a leading cause of myocarditis and pericarditis worldwide, conditions that frequently coexist. Myocarditis were some the early comorbidities associated with SARS-CoV-2 infection COVID-19. Many epidemiologic studies have been conducted since time concluding increased incidence myocarditis/pericarditis at least 15× over pre-COVID levels although condition remains rare. The was reported 1 to 10 cases/100 000 individuals COVID ranging from 150 4000 individuals. Before COVID-19, vaccines in rare cases, but use novel mRNA platforms led higher number cases than previous providing new insight into potential pathogenic mechanisms. COVID-19 vaccine-associated covers large range depending on vaccine platform, age, sex examined. Importantly, findings highlight occurs predominantly male patients aged 12 40 years regardless whether due virus-like or vaccine-a demographic has before This review discusses considering known symptoms, diagnosis, management, treatment, pathogenesis disease gleaned clinical research animal models. Sex differences immune response discussed, theories for how could lead proposed. Additionally, gaps our understanding need further raised.

Language: Английский

Citations

119
Extracellular vesicles as personalized medicine DOI Creative Commons
Danielle J. Beetler, Damian N. Di Florio, Katelyn A. Bruno

et al.

Molecular Aspects of Medicine, Journal Year: 2022, Volume and Issue: 91, P. 101155 - 101155

Published: Nov. 28, 2022

Extracellular vesicles (EVs) are released from all cells in the body, forming an important intercellular communication network that contributes to health and disease. The contents of EVs cell source-specific, inducing distinct signaling responses recipient cells. specificity their accumulation fluid spaces accessible for liquid biopsies make them highly attractive as potential biomarkers therapies duality favorable (therapeutic) or unfavorable (pathological) messengers is context dependent remains be fully determined homeostasis various disease states. This review describes use biomarkers, drug delivery vehicles, regenerative therapeutics, highlighting examples involving viral infections, cancer, neurological diseases. There growing interest provide personalized therapy based on individual patient characteristics. Increasing evidence suggests EV therapeutic approaches ideal medicine due diversity multifunctionality EVs.

Language: Английский

Citations

56
Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems DOI Creative Commons
Alistair V.W. Nunn,

Geoffrey W. Guy,

Wolfgang Brysch

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3113 - 3113

Published: Dec. 2, 2022

Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as "brain fog", fatigue and clotting problems. Explanations for "long COVID" include immune imbalance, incomplete viral clearance potentially, mitochondrial dysfunction. As conditions sub-optimal function are associated initial severity of disease, their prior health could be key in resistance to long COVID recovery. The SARs virus redirects host metabolism towards replication; response, can metabolically react control virus. Resolution is normally achieved after stress activates a hormetic negative feedback mechanism. It therefore possible that, some individuals function, "tip" into chronic inflammatory cycle. This might explain main including platelet Long thus described virally induced self-perpetuating imbalanced non-resolving state characterised by dysfunction, where reactive oxygen species continually drive inflammation shift glycolysis. would suggest that sufferer's needs "tipped" back using stimulus, physical activity, calorie restriction, or chemical compounds mimic these enhancing perhaps combination inhibitors quell response.

Language: Английский

Citations

54
Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19 DOI Creative Commons
Xue Li, Ziqi Zhang, Zhenling Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 13, 2022

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection has dramatically influenced various aspects the world. It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies prevent treat this threatening disease. universally acknowledged that cell death autophagy are essential crucial maintaining host homeostasis participating in pathogenesis. At present, more than twenty different types have been discovered, some parts which fully understood, whereas need investigation. Increasing studies indicated might play an important role virus pathogenicity. However, knowledge interactions related SARS-CoV-2 between lacks systematic elucidation. Therefore, review, we comprehensively delineate how manipulates diverse (including apoptosis, necroptosis, pyroptosis, ferroptosis, NETosis) itself benefits, simultaneously involved occurrence progression COVID-19, aiming provide a reasonable basis existing interventions further development novel therapies.

Language: Английский

Citations

50
NSP4 and ORF9b of SARS-CoV-2 Induce Pro-Inflammatory Mitochondrial DNA Release in Inner Membrane-Derived Vesicles DOI Creative Commons

Md Imam Faizan,

Rituparna Kundu Chaudhuri, Shakti Sagar

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(19), P. 2969 - 2969

Published: Sept. 23, 2022

Circulating cell-free mitochondrial DNA (cf-mtDNA) has been found in the plasma of severely ill COVID-19 patients and is now known as a strong predictor mortality. However, underlying mechanism mtDNA release unexplored. Here, we show novel SARS-CoV-2-mediated pro-inflammatory/pro-apoptotic rational therapeutic stem cell-based approach to mitigate these effects. We systematically screened effects 29 SARS-CoV-2 proteins on damage cell death that NSP4 ORF9b caused extensive structural changes, outer membrane macropore formation, inner vesicles loaded with mtDNA. The macropore-forming ability was mediated through its interaction BCL2 antagonist/killer (BAK), whereas inhibit anti-apoptotic member family protein myeloid leukemia-1 (MCL1) induce vesicle formation containing Knockdown BAK and/or overexpression MCL1 significantly reversed damage. Therapeutically, engineered human mesenchymal cells (MSCs) simultaneous knockdown (MSCshBAK+MCL1) named IMAT-MSCs (intercellular transfer-assisted MSCs). Upon co-culture SARS-CoV-2-infected or NSP4/ORF9b-transduced airway epithelial cells, displayed functional intercellular transfer (IMT) via tunneling nanotubes (TNTs). donation by attenuated pro-inflammatory pro-apoptotic from co-cultured cells. Our findings thus provide new mechanistic basis for SARS-CoV-2-induced engineering MSCs treatment COVID-19.

Language: Английский

Citations

44
SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia DOI Creative Commons
Stephen L. Archer, Asish Dasgupta,

Kuang‐Hueih Chen

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 58, P. 102508 - 102508

Published: Oct. 13, 2022

Language: Английский

Citations

39
The role of cell death in SARS-CoV-2 infection DOI Creative Commons

Cui Yuan,

Zhenling Ma,

Jiufeng Xie

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 20, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed disease 2019 (COVID-19). COVID-19 cases often experience distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death infected cells. Cell mechanisms have a vital role maintaining suitable environment to achieve normal functionality. Nonetheless, these processes are dysregulated, potentially contributing pathogenesis. Over the past decades, multiple pathways becoming better understood. Growing evidence suggests that induction by may significantly contributes infection pathogenicity. However, interaction SARS-CoV-2 with death, together its associated mechanisms, is yet be elucidated. In this review, we summarize existing concerning molecular modulation as well viral-host interactions, shed new light on antiviral therapy against SARS-CoV-2.

Language: Английский

Citations

39
Expanding roles of BCL-2 proteins in apoptosis execution and beyond DOI Open Access
Louise King, Lisa Hohorst, Ana J. García‐Sáez

et al.

Journal of Cell Science, Journal Year: 2023, Volume and Issue: 136(22)

Published: Nov. 15, 2023

ABSTRACT The proteins of the BCL-2 family are known as key regulators apoptosis, with interactions between members determining permeabilisation mitochondrial outer membrane (MOM) and subsequent cell death. However, exact mechanism through which they form apoptotic pore responsible for MOM (MOMP), structure specific components this pore, what roles play outside directly regulating MOMP incompletely understood. Owing to link apoptosis dysregulation disease, important targets drug development. With development clinical use drugs targeting showing success in multiple haematological malignancies, enhancing efficacy these drugs, or indeed developing novel is great interest treat cancer patients who have developed resistance suffer other disease types. Here, we review our current understanding molecular MOMP, a particular focus on recently discovered beyond, discuss implications functions might both healthy tissues disease.

Language: Английский

Citations

24
SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis DOI Open Access
Rushikesh Deshpande, Wangyang Li,

Tiao Li

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1157 - 1157

Published: Jan. 18, 2024

The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. airway is primary target in severe acute respiratory distress syndrome 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks exposure. viral factors that contribute to remain incompletely understood. Thus, this study investigated role open reading frame 7b (Orf7b), an accessory protein virus, causing injury. In screening proteins, we identified Orf7b as one major mediates epithelial death. Overexpression leads apoptosis ferroptosis cells, inhibitors ablate Orf7b-induced upregulates transcription regulator, c-Myc, which integral activation pathways. Depletion c-Myc alleviates both apoptotic ferroptotic deaths mouse models. Our suggests a attributable COVID-19 exposure, supporting it potential therapeutic target.

Language: Английский

Citations

15