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1.
Front Immunol ; 14: 1082191, 2023.
Article in English | MEDLINE | ID: covidwho-2249096

ABSTRACT

Despite recent advances in the research on oncolytic viruses (OVs), a better understanding of how to enhance their replication is key to improving their therapeutic index. Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. The VSV-Δ51 oncolytic virus has been widely used as an anticancer agent with a high selectivity profile. In this study, we examined the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production and oncolytic activity. To test this hypothesis, we first generated a novel VSV-Δ51 mutant that encoded the SARS-COV-2 RBD and compared viral spreading and viral yield between VSV-Δ51-RBD and VSV-Δ51 in vitro. Using the viral plaque assay, we demonstrated that the presence of the SARS-CoV-2 RBD in the VSV-Δ51 genome is associated with a significantly larger viral plaque surface area and significantly higher virus titers. Subsequently, using an ATP release-based assay, we demonstrated that the SARS-CoV-2 RBD could enhance VSV-Δ51 oncolytic activity in vitro. This observation was further supported using the B16F10 tumor model. These findings highlighted a novel use of the SARS-CoV-2 RBD as an anticancer agent.


Subject(s)
COVID-19 , Oncolytic Virotherapy , Oncolytic Viruses , Vesicular Stomatitis , Animals , Humans , SARS-CoV-2 , Carrier Proteins/metabolism , Cell Line, Tumor , COVID-19/therapy , Vesicular stomatitis Indiana virus/genetics , Oncolytic Viruses/genetics
2.
Cells ; 11(3)2022 01 29.
Article in English | MEDLINE | ID: covidwho-1667054

ABSTRACT

The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) are currently utilized in clinics for pulmonary inflammatory diseases, including acute respiratory distress syndrome and acute lung injury. Given that MSCs offer a promising treatment against COVID-19, they are being used against COVID-19 in more than 70 clinical trials with promising findings. Genetically engineered MSCs offer promising therapeutic options in pulmonary diseases. However, their potential has not been explored yet. In this review, we provide perspectives on the functionally modified MSCs that can be developed and harnessed for COVID-19 therapy. Options to manage the SARS-CoV-2 infection and its variants using various bioengineering tools to increase the therapeutic efficacy of MSCs are highlighted.


Subject(s)
Bioengineering/methods , COVID-19/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/epidemiology , COVID-19/virology , Cytokines/metabolism , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Mesenchymal Stem Cells/cytology , Pandemics/prevention & control , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Treatment Outcome
4.
Computers, Materials, & Continua ; 68(1):1219-1233, 2021.
Article in English | ProQuest Central | ID: covidwho-1168455

ABSTRACT

Graph colouring is the system of assigning a colour to each vertex of a graph. It is done in such a way that adjacent vertices do not have equal colour. It is fundamental in graph theory. It is often used to solve real-world problems like traffic light signalling, map colouring, scheduling, etc. Nowadays, social networks are prevalent systems in our life. Here, the users are considered as vertices, and their connections/interactions are taken as edges. Some users follow other popular users’ profiles in these networks, and some don’t, but those non-followers are connected directly to the popular profiles. That means, along with traditional relationship (information flowing), there is another relation among them. It depends on the domination of the relationship between the nodes. This type of situation can be modelled as a directed fuzzy graph. In the colouring of fuzzy graph theory, edge membership plays a vital role. Edge membership is a representation of flowing information between end nodes of the edge. Apart from the communication relationship, there may be some other factors like domination in relation. This influence of power is captured here. In this article, the colouring of directed fuzzy graphs is defined based on the influence of relationship. Along with this, the chromatic number and strong chromatic number are provided, and related properties are investigated. An application regarding COVID-19 infection is presented using the colouring of directed fuzzy graphs.

5.
Stem Cells ; 39(6): 707-722, 2021 06.
Article in English | MEDLINE | ID: covidwho-1121521

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has grown to be a global public health crisis with no safe and effective treatments available yet. Recent findings suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus pathogen that causes COVID-19, could elicit a cytokine storm that drives edema, dysfunction of the airway exchange, and acute respiratory distress syndrome in the lung, followed by acute cardiac injury and thromboembolic events leading to multiorgan failure and death. Mesenchymal stem cells (MSCs), owing to their powerful immunomodulatory abilities, have the potential to attenuate the cytokine storm and have therefore been proposed as a potential therapeutic approach for which several clinical trials are underway. Given that intravenous infusion of MSCs results in a significant trapping in the lung, MSC therapy could directly mitigate inflammation, protect alveolar epithelial cells, and reverse lung dysfunction by normalizing the pulmonary microenvironment and preventing pulmonary fibrosis. In this review, we present an overview and perspectives of the SARS-CoV-2 induced inflammatory dysfunction and the potential of MSC immunomodulation for the prevention and treatment of COVID-19 related pulmonary disease.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Mesenchymal Stem Cells/immunology , SARS-CoV-2/immunology , COVID-19/therapy , COVID-19/virology , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Humans , Immunomodulation , Lung/immunology , Lung/pathology , Lung/virology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/virology , Pandemics , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/therapy , Pulmonary Fibrosis/virology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2/genetics
6.
Mathematical Problems in Engineering ; : 1-10, 2020.
Article | Academic Search Complete | ID: covidwho-830927

ABSTRACT

Coloring of graph theory is widely used in different fields like the map coloring, traffic light problems, etc. Hypergraphs are an extension of graph theory where edges contain single or multiple vertices. This study analyzes cluster hypergraphs where cluster vertices too contain simple vertices. Coloring of cluster networks where composite/cluster vertices exist is done using the concept of coloring of cluster hypergraphs. Proper coloring and strong coloring of cluster hypergraphs have been defined. Along with these, local coloring in cluster hypergraphs is also provided. Such a cluster network, COVID19 affected network, is assumed and colored to visualize the affected regions properly. [ABSTRACT FROM AUTHOR] Copyright of Mathematical Problems in Engineering is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

7.
Sci Adv ; 6(30): eaba6884, 2020 07.
Article in English | MEDLINE | ID: covidwho-706017

ABSTRACT

More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , Pneumonia, Viral/therapy , Batch Cell Culture Techniques/methods , Bioreactors , COVID-19 , Coronavirus Infections/virology , Graft vs Host Disease/therapy , Humans , Metabolic Engineering/methods , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Transplant Recipients
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