scholarly journals Myocardial Damage by SARS-CoV-2: Emerging Mechanisms and Therapies

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1880
Author(s):  
Huyen Tran Ho ◽  
Stefan Peischard ◽  
Nathalie Strutz-Seebohm ◽  
Karin Klingel ◽  
Guiscard Seebohm
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Energy Metabolism ◽  
Programmed Cell Death ◽  
Viral Replication ◽  
Ion Homeostasis ◽  
Membrane Vesicles ◽  
Cardiac Cells ◽  
The Body ◽  
Double Membrane

Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can lead to myocarditis and an outline of potential treatment options. The main points are: (1) Viral entry: SARS-CoV-2 uses specific receptors and proteases for docking and priming in cardiac cells. Thus, different receptors or protease inhibitors might be effective in SARS-CoV-2-infected cardiac cells. (2) Viral replication: SARS-CoV-2 uses RNA-dependent RNA polymerase for replication. Drugs acting against ssRNA(+) viral replication for cardiac cells can be effective. (3) Autophagy and double-membrane vesicles: SARS-CoV-2 manipulates autophagy to inhibit viral clearance and promote SARS-CoV-2 replication by creating double-membrane vesicles as replication sites. (4) Immune response: Host immune response is manipulated to evade host cell attacks against SARS-CoV-2 and increased inflammation by dysregulating immune cells. Efficiency of immunosuppressive therapy must be elucidated. (5) Programmed cell death: SARS-CoV-2 inhibits programmed cell death in early stages and induces apoptosis, necroptosis, and pyroptosis in later stages. (6) Energy metabolism: SARS-CoV-2 infection leads to disturbed energy metabolism that in turn leads to a decrease in ATP production and ROS production. (7) Viroporins: SARS-CoV-2 creates viroporins that lead to an imbalance of ion homeostasis. This causes apoptosis, altered action potential, and arrhythmia.

scholarly journals Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 194
Author(s):  
Jutta Ries ◽  
Abbas Agaimy ◽  
Falk Wehrhan ◽  
Christoph Baran ◽  
Stella Bolze ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Malignant Transformation ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Precancerous Lesions ◽  
Death Receptor ◽  
Oral Leukoplakia ◽  
Significant Difference

Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated. However, little is known about its expression in oral precancerous lesions like oral leukoplakia (OLP). The aim of the study was to investigate whether an increased expression of PD-1/PD-L1 already exists in OLP and whether it is associated with malignant transformation. Material and Methods: PD-1 and PD-L1 expression was immunohistologically analyzed separately in the epithelium (E) and the subepithelium (S) of OLP that had undergone malignant transformation within 5 years (T-OLP), in OLP without malignant transformation (N-OLP), in corresponding OSCC and in NOM. Additionally, RT-qPCR analysis for PD-L1 expression was done in the entire tissues. Additionally, the association between overexpression and malignant transformation, dysplasia and inflammation were examined. Results: Compared to N-OLP, there were increased levels of PD-1 protein in the epithelial and subepithelial layers of T-OLP (pE = 0.001; pS = 0.005). There was no significant difference in PD-L1 mRNA expression between T-OLP and N-OLP (p = 0.128), but the fold-change increase between these groups was significant (Relative Quantification (RQ) = 3.1). In contrast to N-OLP, the PD-L1 protein levels were significantly increased in the epithelial layers of T-OLP (p = 0.007), but not in its subepithelial layers (p = 0.25). Importantly, increased PD-L1 levels were significantly associated to malignant transformation within 5 years. Conclusion: Increased levels of PD-1 and PD-L1 are related to malignant transformation in OLP and may represent a promising prognostic indicator to determine the risk of malignant progression of OLP. Increased PD-L1 levels might establish an immunosuppressive microenvironment, which could favor immune escape and thereby contribute to malignant transformation. Hence, checkpoint inhibitors could counteract tumor development in OLP and may serve as efficient therapeutic strategy in patients with high-risk precancerous lesions.

Combination of DNA demethylation and chemotherapy to trigger cell pyroptosis for inhalation treatment of lung cancer

Nanoscale ◽  
2021 ◽  
Author(s):  
Beibei Xie ◽  
Tingting Liu ◽  
Shuang Chen ◽  
Yan Zhang ◽  
Dongxian He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Effective Means ◽  
Dna Demethylation ◽  
Local Immune Response ◽  
Anticancer Efficacy

Pyroptosis is an inflammation-dependent and self-cascade amplifying type of programmed cell death, serving as an effective means for activating the local immune response and improving the anticancer efficacy. As the...

scholarly journals Double-Membrane Vesicles as Platforms for Viral Replication

2020 ◽  
Vol 28 (12) ◽  
pp. 1022-1033 ◽  
Author(s):  
Georg Wolff ◽  
Charlotte E. Melia ◽  
Eric J. Snijder ◽  
Montserrat Bárcena
Keyword(s):  
Viral Replication ◽  
Membrane Vesicles ◽  
Double Membrane

scholarly journals Pyknotic chromatin in mitonucleons elevating in syncytia undergo karyorhhexis and karyolysis before coalescing into an irregular chromatin mass: Differentiation of Ishikawa Domes, Part 2

2016 ◽  
Author(s):  
Honoree Fleming
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Programmed Cell Death ◽  
Apical Membrane ◽  
Driving Forces ◽  
Double Membrane ◽  
Membrane Staining ◽  
Fragmented Dna ◽  
Endogenous Biotin ◽  
Irregular Mass

Pyknosis, karyorrhexis and karyolysis, harbingers of programmed cell death in many systems, appear to be driving forces that transform Ishikawa monolayer epithelial cells into differentiated dome cells. The heterochromatin affected by these process is contained in multiple nuclei aggregated in the syncytia that form when Ishikawa monolayers are stimulated to differentiate (Fleming, 2016a). The nuclear aggregates are enveloped in a double membrane staining for the endogenous biotin in mitochondrial carboxylases. The structure called a mitonucleon becomes vacuolated, along with the heterochromatin it envelops, and this structure elevates with the apical membrane of the syncytium 6 to 8 hours into the 20 hour differentiation, becoming increasingly pyknotic. This phase of the differentiation comes to an end when the mitonucleon membranes are breached and nuclei emerging from the aggregated state can be seen to fragment explosively. Fragmented DNA associates with an array of microtubules, filling the large central clearing of the predome. Some chromatin remains unfragmented and can be seen of the edges of the predome clearing. Cell death does not occur. Instead, the fragmented DNA coalesces into an irregular mass within the apical and basal membranes of the predome under which fluid has been accumulating. From the chromatin sheet, nuclei emerge amitotically as described in Part 3 of this series (Fleming, 2016c).

scholarly journals Pyknotic chromatin in mitonucleons elevating in syncytia undergo karyorhhexis and karyolysis before coalescing into an irregular chromatin mass: Differentiation of Ishikawa Domes, Part 2

2016 ◽  
Author(s):  
Honoree Fleming
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Programmed Cell Death ◽  
Apical Membrane ◽  
Driving Forces ◽  
Double Membrane ◽  
Membrane Staining ◽  
Fragmented Dna ◽  
Endogenous Biotin ◽  
Irregular Mass

Pyknosis, karyorrhexis and karyolysis, harbingers of programmed cell death in many systems, appear to be driving forces that transform Ishikawa monolayer epithelial cells into differentiated dome cells. The heterochromatin affected by these process is contained in multiple nuclei aggregated in the syncytia that form when Ishikawa monolayers are stimulated to differentiate (Fleming, 2016a). The nuclear aggregates are enveloped in a double membrane staining for the endogenous biotin in mitochondrial carboxylases. The structure called a mitonucleon becomes vacuolated, along with the heterochromatin it envelops, and this structure elevates with the apical membrane of the syncytium 6 to 8 hours into the 20 hour differentiation, becoming increasingly pyknotic. This phase of the differentiation comes to an end when the mitonucleon membranes are breached and nuclei emerging from the aggregated state can be seen to fragment explosively. Fragmented DNA associates with an array of microtubules, filling the large central clearing of the predome. Some chromatin remains unfragmented and can be seen of the edges of the predome clearing. Cell death does not occur. Instead, the fragmented DNA coalesces into an irregular mass within the apical and basal membranes of the predome under which fluid has been accumulating. From the chromatin sheet, nuclei emerge amitotically as described in Part 3 of this series (Fleming, 2016c).

scholarly journals Programmed cell death-ligand 2: A neglected but important target in the immune response to cancer?

2020 ◽  
Vol 13 (10) ◽  
pp. 100811 ◽  
Author(s):  
Cinzia Solinas ◽  
Marco Aiello ◽  
Esdy Rozali ◽  
Matteo Lambertini ◽  
Karen Willard-Gallo ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Important Target ◽  
Immune Response To Cancer

scholarly journals COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

2020 ◽  
Vol 2020 ◽  
pp. 1-34
Author(s):  
Patrick C. Bradshaw ◽  
William A. Seeds ◽  
Alexandra C. Miller ◽  
Vikrant R. Mahajan ◽  
William M. Curtis
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
T Cell ◽  
Energy Metabolism ◽  
Respiratory Distress ◽  
Ketogenic Diet ◽  
Innate Immune Response ◽  
Redox State ◽  
Innate Immune ◽  
Cytokine Storm

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.

scholarly journals Emerging Proviral Roles of Caspases during Lytic Replication of Gammaherpesviruses

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Tate Tabtieng ◽  
Marta M. Gaglia
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Viral Replication ◽  
Immune Evasion ◽  
Lytic Replication ◽  
Growing Body

ABSTRACTDue to their roles in the regulation of programmed cell death and inflammation, the cellular caspase proteases are considered antiviral factors. However, recent studies have revealed examples of proviral functions for caspases. Here, we review a growing body of literature on the role of caspases in promoting the replication of human gammaherpesviruses. We propose that gammaherpesviruses have evolved ways to redirect these enzymes and to use their activation to support viral replication and immune evasion.

scholarly journals Plant Mitophagy in Comparison to Mammals: What Is Still Missing?

2021 ◽  
Vol 22 (3) ◽  
pp. 1236
Author(s):  
Kaike Ren ◽  
Lanlan Feng ◽  
Shuangli Sun ◽  
Xiaohong Zhuang
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Plant Cells ◽  
Molecular Evidence ◽  
Double Membrane ◽  
Mitochondrial Homeostasis ◽  
A Cell ◽  
Mitochondrial Number

Mitochondrial homeostasis refers to the balance of mitochondrial number and quality in a cell. It is maintained by mitochondrial biogenesis, mitochondrial fusion/fission, and the clearance of unwanted/damaged mitochondria. Mitophagy represents a selective form of autophagy by sequestration of the potentially harmful mitochondrial materials into a double-membrane autophagosome, thus preventing the release of death inducers, which can trigger programmed cell death (PCD). Recent advances have also unveiled a close interconnection between mitophagy and mitochondrial dynamics, as well as PCD in both mammalian and plant cells. In this review, we will summarize and discuss recent findings on the interplay between mitophagy and mitochondrial dynamics, with a focus on the molecular evidence for mitophagy crosstalk with mitochondrial dynamics and PCD.

Sign in / Sign up

Export Citation Format

Share Document