scholarly journals Plasma S-Adenosylmethionine Is Associated with Lung Injury in COVID-19

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Evgeny Vladimirovich Kryukov ◽  
Alexander Vladimirovich Ivanov ◽  
Vladimir Olegovich Karpov ◽  
Valery Vasil’evich Aleksandrin ◽  
Alexander Mikhaylovich Dygai ◽  
...  
Keyword(s):  
Lung Injury ◽  
Negative Association ◽  
Lung Damage ◽  
Glutathione Level ◽  
Methylation Index ◽  
Potential Marker ◽  
Damage Risk ◽  
And Oxidative Stress ◽  
Cytokine Imbalance

Objective. S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are indicators of global transmethylation and may play an important role as markers of severity of COVID-19. Methods. The levels of plasma SAM and SAH were determined in patients admitted with COVID-19 ( n = 56 , mean   age = 61 ). Lung injury was identified by computed tomography (CT) in accordance with the CT0-4 classification. Results. SAM was found to be a potential marker of lung damage risk in COVID-19 patients ( SAM > 80   nM ; CT3,4 vs. CT 0-2: relative ratio (RR) was 3.0; p = 0.0029 ). SAM / SAH > 6.0 was also found to be a marker of lung injury (CT2-4 vs. CT0,1: RR = 3.47 , p = 0.0004 ). There was a negative association between SAM and glutathione level ( ρ = − 0.343 , p = 0.011 ). Interleukin-6 (IL-6) levels were associated with SAM ( ρ = 0.44 , p = 0.01 ) and SAH ( ρ = 0.534 , p = 0.001 ) levels. Conclusions. A high SAM level and high methylation index are associated with the risk of lung injury in patients with COVID-19. The association of SAM with IL-6 and glutathione indicates an important role of transmethylation in the development of cytokine imbalance and oxidative stress in patients with COVID-19.

scholarly journals Plasma S-Adenosylmethionine is Associated with Lung Injury in COVID-19

2021 ◽  
Author(s):  
Evgeny Kryukov ◽  
Alexander Ivanov ◽  
Vladimir Karpov ◽  
Valery Alexandrin ◽  
Alexander Dygai ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Injury ◽  
Interleukin 6 ◽  
Lung Damage ◽  
Methylation Index ◽  
Relative Ratio ◽  
Potential Marker ◽  
Damage Risk ◽  
Cytokine Imbalance

AbstractObjectiveS-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are indicators of global transmethylation and may play an important role as markers of severity of COVID-19.MethodsThe levels of plasma SAM and SAH were determined in patients admitted with COVID-19 (n = 56, mean age = 61). Lung injury was identified by computed tomography (CT) in accordance with the CT0-4 classification.ResultsSAM was found to be a potential marker of lung damage risk in COVID-19 patients (SAM > 80 nM; CT3,4 vs. CT 0-2: relative ratio (RR) was 3.0; p = 0.0029). SAM/SAH > 6.0 was also found to be a marker of lung injury (CT2-4 vs. CT0,1: RR = 3.47, p = 0.0004). Interleukin-6 (IL-6) levels were associated with SAM (ρ = 0.44, p = 0.01) and SAH (ρ = 0.534, p = 0.001) levels.ConclusionsHigh SAM levels and high methylation index are associated with the risk of lung injury in COVID-19 patients. The association of SAM and SAH with IL-6 indicates an important role of transmethylation in the development of cytokine imbalance in COVID-19 cases.

scholarly journals NADPH Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model

2021 ◽  
Author(s):  
Sang Hoon Lee ◽  
Mi Hwa Shin ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Kyung Soo Chung ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Control Group ◽  
Group 4 ◽  
Ventilator Induced Lung Injury ◽  
Cell Counts ◽  
Group 5 ◽  
Group 2

Abstract For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. We investigated the role of NOX4 in a ventilator-induced lung injury (VILI) model.Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p<0.001). NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the ICU.In the VILI model, it may be possible to block VILI using NOX4 antibodies.

The Role of Recipient Platelets In the Prevention of Antibody-Mediated Transfusion Related Acute Lung Injury (TRALI)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3351-3351
Author(s):  
Yuhan Chen ◽  
Michael Kim ◽  
Arata Tabuchi ◽  
Wolfgang M. Kuebler ◽  
Rukhsana Aslam ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Conflicts Of Interest ◽  
Scid Mice ◽  
Lung Damage ◽  
Cell Mediated Immunity ◽  
Shock Lung ◽  
Inflammatory Milieu ◽  
Platelet Depletion

Abstract Abstract 3351 Transfusion related acute lung injury (TRALI) is a serious complication of transfusion. The pathogenesis of TRALI is not fully understood but previous findings have suggested that platelet depletion can protect mice in a two-hit model of TRALI (Looney et al J Clin Invest 119:3450, 2009). To further understand the role of platelets in preventing antibody-mediated TRALI, two mouse models of immune thrombocytopenia (ITP) were utilized. In the passive ITP model, SCID mice were injected with a monoclonal anti-platelet antibody (MWReg30) intraperitoneally (ip, 18 h before TRALI induction) or intravenously (iv, 2 h before TRALI induction). In the active ITP model, SCID mice were transferred with splenocytes from anti-CD61 immune GPIIIa-knockout mice and thrombocytopenia occurred within 2 weeks post transfer (Chow et al Blood 115;1247, 2010). TRALI induction was performed by injecting the various thrombocytopenic SCID mice with a murine monoclonal MHC class I antibody (mAb, 34-1 -2s) iv and several parameters were observed for up to 2 h post antibody injection. In control, non-thrombocytopenic SCID mice, 34-1 -2s injection caused severe systemic shock as noted by reduced rectal temperatures which was associated with significant lung damage and mortality (45%) within 1 hour of 34-1 -2s infusion as previously shown (Fung et al. Blood DOI 10.1182/blood-2010-05-284570). In contrast, while SCID mice depleted of platelets by the passive ip route had systemic shock, lung damage and a 60% mortality rate, those mice made thrombocytopenic by the iv route were completely protected from mortality. On the other hand, in the active ITP model, where the induced thrombocytopenia is associated with a proinflammatory anti-platelet immune response, no mortality was observed in those mice made thrombocytopenic by antibody-mediated immune mechanisms whereas 80% of mice rendered thrombocytopenic by CD8+ T cell-mediated immunity were dead within 1 hr post 34-1 -2s infusion. These results suggest that thrombocytopenia in itself does not protect against antibody-mediated TRALI severity but the nature of the thrombocytopenia induction (e.g. acute passive iv infusion or active ITP immune transfer) is important. In fact, depending on the inflammatory milieu associated with the thrombocytopenia, platelets may actually increase the severity of TRALI. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Endothelial Dysfunction, Inflammation, and Oxidative Stress in COVID-19—Mechanisms and Therapeutic Targets

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Adriana Fodor ◽  
Brandusa Tiperciuc ◽  
Cezar Login ◽  
Olga H. Orasan ◽  
Andrada L. Lazar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Respiratory Failure ◽  
Endothelial Dysfunction ◽  
Clinical Manifestations ◽  
Therapeutic Targets ◽  
Lung Damage ◽  
Wide Range ◽  
Underlying Mechanisms ◽  
And Oxidative Stress

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.

scholarly journals NADPH Oxidase 4 Signaling in a Ventilator-Induced Lung Injury Mouse Model

2020 ◽  
Author(s):  
Sang Hoon Lee ◽  
Mi Hwa Shin ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Kyung Soo Chung ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Control Group ◽  
Nadph Oxidase 4 ◽  
Ventilator Induced Lung Injury ◽  
Oxygen Fraction ◽  
Cell Counts ◽  
The Relationship

Abstract BackgroundFor patients with acute respiratory distress syndrome (ARDS), a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 in lung injury using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model.MethodsWild-type male C57BL/6J mice and NOX4 KO male mice were divided into five groups: (1) control group: wild-type (WT) mice + non-ventilator; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group: NOX4 KO + non-ventilator; (4) NOX4 KO with HTV group: NOX4 KO mice + HTV; (5) NOX4 inhibitor group: WT mice + HTV + post-treatment (anti-GKT 137831 inhibitor). In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 μL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.ResultsCell counts from BALFs were significantly lower (p<0.01) in the NOX4 KO with HTV group compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO mouse group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (both, p<0.001). In patients with respiratory disease, NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit.ConclusionsIn the VILI model, NOX4 expression is significantly associated with Eph-ephrin signaling. It may be possible to block VILI using NOX4 antibodies.

scholarly journals Impaired Glucocorticoid Receptor Signaling Aggravates Lung Injury after Hemorrhagic Shock

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 112
Author(s):  
Jonathan M. Preuss ◽  
Ute Burret ◽  
Michael Gröger ◽  
Sandra Kress ◽  
Angelika Scheuerle ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Lung Damage ◽  
Lung Mechanics ◽  
Cytokine Signaling ◽  
Pro Inflammatory Cytokines

We previously showed that attenuated lung injury after hemorrhagic shock (HS) coincided with enhanced levels of the glucocorticoid (GC) receptor (GR) in lung tissue of swine. Here, we investigated the effects of impaired GR signaling on the lung during resuscitated HS using a dysfunctional GR mouse model (GRdim/dim). In a mouse intensive care unit, HS led to impaired lung mechanics and aggravated lung inflammation in GRdim/dim mice compared to wildtype mice (GR+/+). After HS, high levels of the pro-inflammatory and pro-apoptotic transcription factor STAT1/pSTAT1 were found in lung samples from GRdim/dim mice. Lungs of GRdim/dim mice revealed apoptosis, most likely as consequence of reduced expression of the lung-protective Angpt1 compared to GR+/+ after HS. RNA-sequencing revealed increased expression of pro-apoptotic and cytokine-signaling associated genes in lung tissue of GRdim/dim mice. Furthermore, high levels of pro-inflammatory cytokines and iNOS were found in lungs of GRdim/dim mice. Our results indicate impaired repression of STAT1/pSTAT1 due to dysfunctional GR signaling in GRdim/dim mice, which leads to increased inflammation and apoptosis in the lungs. These data highlight the crucial role of functional GR signaling to attenuate HS-induced lung damage.

scholarly journals Glucocorticoids aggravate hyperoxia-induced lung injury through decreased nuclear factor-κB activity

2003 ◽  
Vol 284 (1) ◽  
pp. L197-L204 ◽  
Author(s):  
Constance Barazzone-Argiroffo ◽  
Alessandra Pagano ◽  
Cristiana Juge ◽  
Isabelle Métrailler ◽  
Anne Rochat ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Nuclear Factor Κb ◽  
Lung Damage ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Lung Weight ◽  
Cell Content ◽  
Adrenal Response

We previously reported that exposure of mice to hyperoxia is characterized by extensive lung cell necrosis and apoptosis, mild inflammatory response, and elevated circulating levels of corticosterone. Administration of hydroxycortisone acetate during hyperoxia aggravated lung injury. Using adrenalectomized (ADX) and sham-operated (sham) mice, we studied the role of the glucocorticoids in hyperoxia-induced lung injury. Lung damage was attenuated in ADX mice as measured by lung weight and protein and cell content in bronchoalveolar lavage and as seen by light microscopy. Mortality was delayed by 10 h. Nuclear factor-κB (NF-κB) activity was significantly decreased in lungs of sham mice exposed to hyperoxia but was preserved in ADX mice. There was a correlation between NF-κB activity in ADX mice and decreased levels of IκBα. In contrast, activator protein-1 activity increased similarly in both groups of mice. Levels of interleukin-6 (IL-6), a transcriptional target of NF-κB, were higher in bronchoalveolar lavage and serum of ADX than sham mice. However, the protective effect of ADX was not mediated by IL-6, because administration of recombinant human IL-6 to sham mice did not prevent lung damage. These results demonstrate that the adrenal response aggravates alveolar injury and is likely to be mediated by the decrease of NF-κB function involved in cell survival.

scholarly journals Protective Role of Surfactant Protein-D Against Lung Injury and Oxidative Stress Induced by Nitrogen Mustard

2018 ◽  
Author(s):  
Vasanthi R Sunil ◽  
Kinal N Vayas ◽  
Jessica A Cervelli ◽  
Elena V Ebramova ◽  
Andrew J Gow ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Nitrogen Mustard ◽  
Surfactant Protein ◽  
Protective Role ◽  
Surfactant Protein D ◽  
And Oxidative Stress

scholarly journals miR-19a-3p inhibition alleviates sepsis-induced lung injury via enhancing USP13 expression

2021 ◽  
Author(s):  
Hangqi Ren ◽  
Wei Mu ◽  
Qiaolian Xu
Keyword(s):  
Lung Injury ◽  
Cell Model ◽  
Lung Damage ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Regulation Mechanism ◽  
Tnf Α ◽  
And Control ◽  
Relationship Of

Sepsis is a systemic inflammatory response syndrome caused by various pathogenic microorganisms or toxins. Lung damage is one of the causes of death in patients with sepsis. This study aimed to investigate the role of miR-19a-3p and its regulation mechanism in sepsis-induced lung injury. MH-S cells were treated with lipopolysaccharide (LPS) to establish sepsis-induced lung injury cell model. C57BL/6 mice were injected with miR-19a-3p antagomiR and LPS to construct animal model. LPS-treated and control cells were transfected with miR-19a-3p mimic, miR-19a-3p inhibitor or USP13 expression vector . The expression levels of miR-19a-3p and USP13 were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The concentration of inflammatory cytokines was measured with enzyme-linked immunosorbent assay (ELISA). The relationship of miR-19a-3p and USP13 was validated using dual-luciferase reporter assay. The lung damage was assessed with hematoxylin-eosin staining (HE). The results showed that LPS treatment increased the concentration of TNF-α, IL-6 and IL-1β in MH-S cells. In LPS treated MH-S cells, the level of miR-19a-3p gradually increased over time. Both miR-19a-3p knockdown and USP13 overexpression in MH-S cells inhibited the LPS-induced production of TNF-α, IL-6 and IL-1β. Moreover, miR-19a-3p negatively regulated the expression of USP13 in MH-S cells. Furthermore, miR-19a-3p inhibitor suppressed lung damage in sepsis model mice. In conclusion, miR-19a-3p knockdown could alleviate sepsis-induced lung injury through enhancing USP13 expression.

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

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