scholarly journals Phytochemicals as Potential Therapeutics for SARS-CoV-2–Induced Cardiovascular Complications: Thrombosis and Platelet Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Samir K. Beura ◽  
Abhishek R. Panigrahi ◽  
Pooja Yadav ◽  
Sunil K. Singh

After gaining entry through ACE2 aided by TMPRSS2, the SARS-CoV-2 causes serious complications of the cardiovascular system leading to myocarditis and other myocardial injuries apart from causing lung, kidney and brain dysfunctions. Here in this review, we are going to divulge the cellular and immunological mechanisms behind the cardiovascular, thrombotic and platelet impairments that are caused in COVID-19. In addition, we also propose the significance of various anti-platelet and anti-thrombotic phytochemicals in the treatment of COVID-19. The virus induces many immune-modulatory cytokines and chemokines which help in the intravascular coagulation and create a pro-thrombotic environment along with pulmonary embolism and thrombocytopenia. Different types of innate and adaptive immune cells and their granular contents regulate the pathophysiology of SARS-CoV-2 induced endothelial and platelet dysfunctions which correlate the involvement of platelets with myocardial injury and intravascular thrombi directly or indirectly. Hence, by exploiting the natural bioactive compounds from medicinal plants and inhibiting the platelet mediated thrombus formation can be beneficial for the treatment of SARS-CoV-2 infection.

Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo

Background: Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. Objectives: The participation of platelets in inflammatory processes will be discussed also in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Conclusion: Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.


2020 ◽  
Vol 2 (2) ◽  
pp. 1-4
Author(s):  
Lawrence M Agius ◽  

Processes of induced generation of auto-reactive lymphocytes are direct consequential formulas in defining profiles of activation and re-activation of immune cells both peripherally and in CNS parenchyma. Such profiles of ongoing transformation include in particular the dimensional reconstitution of both Th1 and Th17 CD4+ lymphocytes within the CNS parenchyma. The dynamics of infiltration and preceding extravasation of immunecompetent cells allows a permissive environment for the actions of cytokines and chemokines in terms specific for the dynamics of stimulated secretion by innate immune cells and of adaptive immune cells. Such integration is defining term of conditioning of permissive micro environmental cues in pathogen-recognition and molecular patterns of recognition of various agonists including bacteria and viruses.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xin Lou ◽  
Juan-Juan Wang ◽  
Ya-Qing Wei ◽  
Jin-Jin Sun

AbstractThe innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at different levels to occur immune evasion, including by N6-methyladenosine (m6A) modification. In this review, we discuss studies revealing the immune evasion mechanism by m6A modification, which underlies the retouching of these signaling networks and the rapid tolerance of innate and adaptive immune molecules during disease. We also focus on the functions of m6A in main chemokines regulation, and their roles in promotive and suppressive immune cell recruitment. We then discuss some of the current challenges in the field and describe future directions for the immunological mechanisms of m6A modification.


2020 ◽  
Vol 21 (21) ◽  
pp. 8151
Author(s):  
Sharda Kumari ◽  
Shibani Mukherjee ◽  
Debapriya Sinha ◽  
Salim Abdisalaam ◽  
Sunil Krishnan ◽  
...  

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.


2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Casey Meizinger ◽  
Bruce Klugherz

Abstract Background While it is understood that coronavirus disease 2019 (COVID-19) is primarily complicated by respiratory failure, more data are emerging on the cardiovascular complications of this disease. A subset of COVID-19 patients present with ST-elevations on electrocardiogram (ECG) yet normal coronary angiography, a presentation that can fit criteria for myocardial infarction with no obstructive coronary atherosclerosis (MINOCA). There is little known about non-coronary myocardial injury observed in patients with COVID-19, and we present a case that should encourage further conversation and study of this clinical challenge. Case summary An 86-year-old man presented to our institution with acute hypoxic respiratory failure and an ECG showing anteroseptal ST-segment elevation concerning for myocardial infarction. Mechanic ventilation was initiated prior to presentation, and emergent transthoracic echocardiography reported an ejection fraction of 50–55%, with no significant regional wall motion abnormalities. Next, emergent coronary angiography was performed, and no significant coronary artery disease was detected. The patient tested positive for COVID-19. Despite supportive management in the intensive care unit, the patient passed away. Discussion We present a case of COVID-19 that is likely associated with MINOCA. It is crucial to understand that in COVID-19 patients with signs of myocardial infarction, not all myocardial injury is due to obstructive coronary artery disease. In the case of COVID-19 pathophysiology, it is important to consider the cardiovascular effects of hypoxic respiratory failure, potential myocarditis, and significant systemic inflammation. Continued surveillance and research on the cardiovascular complications of COVID-19 is essential to further elucidate management and prognosis.


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 634
Author(s):  
Bailee H. Sliker ◽  
Paul M. Campbell

Tumors are composed of not only epithelial cells but also many other cell types that contribute to the tumor microenvironment (TME). Within this space, cancer-associated fibroblasts (CAFs) are a prominent cell type, and these cells are connected to an increase in tumor progression as well as alteration of the immune landscape present in and around the tumor. This is accomplished in part by their ability to alter the presence of both innate and adaptive immune cells as well as the release of various chemokines and cytokines, together leading to a more immunosuppressive TME. Furthermore, new research implicates CAFs as players in immunotherapy response in many different tumor types, typically by blunting their efficacy. Fibroblast activation protein (FAP) and transforming growth factor β (TGF-β), two major CAF proteins, are associated with the outcome of different immunotherapies and, additionally, have become new targets themselves for immune-based strategies directed at CAFs. This review will focus on CAFs and how they alter the immune landscape within tumors, how this affects response to current immunotherapy treatments, and how immune-based treatments are currently being harnessed to target the CAF population itself.


2021 ◽  
pp. 263246362199238
Author(s):  
Julio C. Sauza-Sosa ◽  
Oscar Millan-Iturbe ◽  
Jorge Mendoza-Ramirez ◽  
Carlos N. Velazquez-Gutierrez ◽  
Erika Lizeth De la Cruz Reyna ◽  
...  

Background: Myocardial injury is a common manifestation in patients with coronavirus disease (COVID-19), and the correlation with adverse outcomes has been demonstrated; therefore, adequate monitoring of myocardial injury markers is very important. Case Summary: A patient with COVID-19 was hospitalized in our hospital with an initial classification of intermediate risk for myocardial injury, after serial measurements of myocardial injury markers, risk was readjusted to high, as shown later by electrocardiographic abnormalities. The patient underwent emergency diagnostic coronary angiography and successful angioplasty. The patient was discharged to home. Discussion: Myocardial injury risk-stratification is essential in patients with COVID-19, since it is essential in the recognition of patients who are susceptible to cardiovascular complications.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2500
Author(s):  
Cristina Capuano ◽  
Chiara Pighi ◽  
Simone Battella ◽  
Davide De Federicis ◽  
Ricciarda Galandrini ◽  
...  

Natural killer (NK) cells hold a pivotal role in tumor-targeting monoclonal antibody (mAb)-based activity due to the expression of CD16, the low-affinity receptor for IgG. Indeed, beyond exerting cytotoxic function, activated NK cells also produce an array of cytokines and chemokines, through which they interface with and potentiate adaptive immune responses. Thus, CD16-activated NK cells can concur to mAb-dependent “vaccinal effect”, i.e., the development of antigen-specific responses, which may be highly relevant in maintaining long-term protection of treated patients. On this basis, the review will focus on strategies aimed at potentiating NK cell-mediated antitumor functions in tumor-targeting mAb-based regimens, represented by (a) mAb manipulation strategies, aimed at augmenting recruitment and efficacy of NK cells, such as Fc-engineering, and the design of bi- or trispecific NK cell engagers and (b) the possible exploitation of memory NK cells, whose distinctive characteristics (enhanced responsiveness to CD16 engagement, longevity, and intrinsic resistance to the immunosuppressive microenvironment) may maximize therapeutic mAb antitumor efficacy.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Yu Chen ◽  
Jingang Cui ◽  
Qinbo Yang ◽  
Chenglin Jia ◽  
Minqi Xiong ◽  
...  

Myocardial fibrosis results from cardiac injuries caused by various pathophysiological mechanisms including myocardial infarction, leading to destruction of myocardial architecture and progressive cardiac dysfunction. Oxidative stress is likely involved in myocardial ischemic injury and the subsequent tissue remodeling mediated by myocardial fibrogenesis. Our current study aimed to evaluate the implication of NADPH oxidase in overproduction of reactive oxygen species and its contribution to the pathogenesis of myocardial fibrogenesis after ischemic injuries. The effects of Apocynin, a selective NADPH oxidase inhibitor, were evaluated in the mouse model of isoproterenol-induced myocardial injury by histopathological approaches and whole-genome gene expression profiling. The results demonstrated that Apocynin was able to inhibit the development of ISO-induced myocardial necrotic lesions and fibrogenesis in a dose-dependent manner. Moreover, the preventive effects of Apocynin on myocardial injuries were associated with suppressed expression of genes implicated in inflammation responses and extracellular matrix, which were remarkably upregulated by isoproterenol administration. In summary, o ur study provides proof-of-concept for the involvement of NADPH oxidase-mediated ROS generation in myocardial ischemic injuries and fibrogenesis, which will benefit the mechanism-based therapeutic development targeting NADPH oxidase and oxidative stress in treating myocardial fibrosis and related disorders.


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