scholarly journals Role of miRNAs as biomarkers of COVID-19: a scoping review of the status and future directions for research in this field

2021 ◽  
Author(s):  
Marília B Visacri ◽  
Aline de S Nicoletti ◽  
Eder de C Pincinato ◽  
Pía Loren ◽  
Nicolás Saavedra ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Replication ◽  
Scoping Review ◽  
Literature Search ◽  
Current Status ◽  
Future Directions ◽  
The Status ◽  
Infected Cells ◽  
Potential Biomarkers

Aim: miRNAs are potential biomarkers of several diseases. This review aimed to identify the miRNAs that could serve as biomarkers of COVID-19. Materials & methods: A literature search of nine databases was carried out for studies published before 13 June 2021 that described dysregulated miRNAs in cells or animals infected by SARS-CoV-2 or in patients with COVID-19. Two independent reviewers selected the studies and extracted data; disagreements were resolved by a third reviewer. Results: Twenty studies were included in this scoping review; results suggested that miR-21-5p, miR-146a, miR-126-3p, miR-144 and miR-155 are the most important dysregulated miRNAs that could serve as biomarkers for diagnosing and indicating the severity of COVID-19. miRNAs appear to play key roles in viral replication, proliferation of infected cells, immune response, inflammation and cardiovascular dysfunction. Conclusion: This review provides insights into the role of miRNAs as biomarkers in COVID-19 and the current status and future directions for research in this field.

scholarly journals MicroRNAs as biomarkers of coronavirus disease 2019 (COVID-19): a scoping review

2021 ◽  
Author(s):  
Marília Berlofa Visacri ◽  
Aline de Souza Nicoletti ◽  
Eder de Carvalho Pincinato ◽  
Patricia Moriel
Keyword(s):  
Immune Response ◽  
Scoping Review ◽  
Predictive Biomarkers ◽  
Infectious Agent ◽  
Cochrane Library ◽  
Cell Immune Response ◽  
Eligibility Criteria ◽  
Infected Cells ◽  
Novel Coronavirus

Abstract Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which was identified as the infectious agent responsible for coronavirus disease 2019 (COVID-19). MicroRNAs (miRNAs) are small non-coding RNAs that can be potential biomarkers of several diseases. The aim of this scoping review was to identify which miRNAs could be biomarkers of COVID-19 and their roles. Methods. A literature search was performed based on PubMed, PubMed Central, BVS/BIREME, Web of Science, Scopus, EBSCOhost, ProQuest, Embase, and Cochrane Library for studies published until January 28th, 2021. Animal and human studies that described miRNAs as biomarkers of SARS-CoV-2 infection/COVID-19 were included. Studies with a purely computational approach were excluded. Results. A total of 1,797 records were identified, seven of which met the eligibility criteria. Six studies were conducted in humans (samples derived from blood) and one was performed in an animal model (lung tissue). The most important miRNAs identified were miR-195-5p, miR-618, miR-146a-5p, miR-21-5p, miR-15b-5p, miR-142-3p, miR-155, miR-208a, miR-499, miR-103a-2-5p, miR-200c-3p, miR-2115-3p, and members of the let-7 family. Among these miRNAs, miR-146a-5p, miR-21-5p, miR-15b-5p, and members of the let-7 family may be important as they were deregulated in more than one study. Dysregulated miRNAs appear to play key roles in viral replication, proliferation of infected cells, immune response, inflammation, or cardiovascular dysfunction. Conclusion. MiRNAs may be used as potential diagnostic or severity biomarkers, predictive biomarkers, biomarkers of T-cell immune response, and as therapeutic targets of COVID-19. Further studies are required to investigate and validate the role of miRNAs as biomarkers of COVID-19.

scholarly journals Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle

2021 ◽  
Vol 22 (9) ◽  
pp. 4438
Author(s):  
Jessica Proulx ◽  
Kathleen Borgmann ◽  
In-Woo Park
Keyword(s):  
Immune Response ◽  
Life Cycle ◽  
Deubiquitinating Enzyme ◽  
Deubiquitinating Enzymes ◽  
Antiviral Immune Response ◽  
Cellular Processes ◽  
Virus Life Cycle ◽  
Infected Cells ◽  
Dependent Processes

The ubiquitin (Ub) proteasome system (UPS) plays a pivotal role in regulation of numerous cellular processes, including innate and adaptive immune responses that are essential for restriction of the virus life cycle in the infected cells. Deubiquitination by the deubiquitinating enzyme, deubiquitinase (DUB), is a reversible molecular process to remove Ub or Ub chains from the target proteins. Deubiquitination is an integral strategy within the UPS in regulating survival and proliferation of the infecting virus and the virus-invaded cells. Many viruses in the infected cells are reported to encode viral DUB, and these vial DUBs actively disrupt cellular Ub-dependent processes to suppress host antiviral immune response, enhancing virus replication and thus proliferation. This review surveys the types of DUBs encoded by different viruses and their molecular processes for how the infecting viruses take advantage of the DUB system to evade the host immune response and expedite their replication.

scholarly journals Role of Small Molecule Targeted Compounds in Cancer: Progress, Opportunities, and Challenges

2021 ◽  
Vol 9 ◽  
Author(s):  
Guoqiang Sun ◽  
Dawei Rong ◽  
Zhouxiao Li ◽  
Guangshun Sun ◽  
Fan Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Drug Administration ◽  
Small Molecule ◽  
Molecular Targeted Therapy ◽  
Low Cost ◽  
Future Directions ◽  
Clinical Drug

Research on molecular targeted therapy of tumors is booming, and novel targeted therapy drugs are constantly emerging. Small molecule targeted compounds, novel targeted therapy drugs, can be administered orally as tablets among other methods, and do not draw upon genes, causing no immune response. It is easily structurally modified to make it more applicable to clinical needs, and convenient to promote due to low cost. It refers to a hotspot in the research of tumor molecular targeted therapy. In the present study, we review the current Food and Drug Administration (FDA)-approved use of small molecule targeted compounds in tumors, summarize the clinical drug resistance problems and mechanisms facing the use of small molecule targeted compounds, and predict the future directions of the evolving field.

scholarly journals Genetic diversity of Collaborative Cross mice controls viral replication, clinical severity and brain pathology induced by Zika virus infection, independently of Oas1b

2019 ◽  
Author(s):  
Caroline Manet ◽  
Etienne Simon-Lorière ◽  
Grégory Jouvion ◽  
David Hardy ◽  
Matthieu Prot ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Viral Load ◽  
Viral Replication ◽  
Clinical Severity ◽  
Brain Pathology ◽  
Zikv Infection ◽  
Infected Cells ◽  
Host Genetic ◽  
Host Genes

ABSTRACTThe explosive spread of Zika virus (ZIKV) has been associated with major variations in severe disease and congenital afflictions among infected populations, suggesting an influence of host genes. We investigated how genome-wide variants could impact susceptibility to ZIKV infection in mice. We first describe that the susceptibility of Ifnar1 knockout mice is largely influenced by their genetic background. We then show that the broad genetic diversity of Collaborative Cross mice, which receptor to type I interferon (IFNAR) was blocked by anti-IFNAR antibody, expressed phenotypes ranging from complete resistance to severe symptoms and death with large variations in the peak and rate of decrease of plasma viral load, in brain viral load, in brain histopathology and in viral replication rate in infected cells. Differences of susceptibility between CC strains were correlated between Zika, Dengue and West Nile viruses. We identified highly susceptible and resistant mouse strains as new models to investigate the mechanisms of human ZIKV disease and other flavivirus infections. Genetic analyses revealed that phenotypic variations are driven by multiple genes with small effects, reflecting the complexity of ZIKV disease susceptibility in human population. Notably, our results rule out a role of the Oas1b gene in the susceptibility to ZIKV. Altogether, this study emphasizes the role of host genes in the pathogeny of ZIKV infection and lays the foundation for further genetic and mechanistic studies.IMPORTANCEIn recent outbreaks, ZIKV has infected millions of people and induced rare but potentially severe complications, including Guillain-Barré syndrome and encephalitis in adults. While several viral sequence variants were proposed to enhance the pathogenicity of ZIKV, the influence of host genetic variants in the clinical heterogeneity remains mostly unexplored. We have addressed this question using a mouse panel which models the genetic diversity of human population and a ZIKV strain from a recent clinical isolate. Through a combination of in vitro and in vivo approaches, we demonstrate that multiple host genetic variants determine viral replication in infected cells, and clinical severity, kinetics of blood viral load and brain pathology in mice. We describe new mouse models expressing high susceptibility or resistance to ZIKV and to other flaviviruses. These models will facilitate the identification and mechanistic characterization of host genes that influence ZIKV pathogenesis.

scholarly journals Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication

2020 ◽  
Author(s):  
Christoph C. Carter ◽  
Jean Paul Olivier ◽  
Alexis Kaushansky ◽  
Fred D. Mast ◽  
John D. Aitchison
Keyword(s):  
Viral Replication ◽  
Cell Survival ◽  
Structural Protein ◽  
Protein Protein Interaction ◽  
Mechanistic Target Of Rapamycin ◽  
Promote Cell Survival ◽  
Important Regulator ◽  
Infected Cells ◽  
Induced Apoptosis

ABSTRACTThe mechanistic target of rapamycin (mTOR) functions in at least two distinct complexes: mTORC1, which regulates cellular anabolic-catabolic homeostasis, and mTORC2, which is an important regulator of cell survival and cytoskeletal maintenance. mTORC1 has been implicated in the pathogenesis of flaviviruses including dengue, where it contributes to the establishment of a pro-viral autophagic state. In contrast, the role of mTORC2 in viral pathogenesis is unknown. In this study, we explore the consequences of a physical protein-protein interaction between dengue non-structural protein 5 (NS5) and host cell mTOR proteins during infection. Using shRNA to differentially target mTORC1 and mTORC2 complexes, we show that mTORC2 is required for optimal dengue replication. Furthermore, we show that mTORC2 is activated during viral replication, and that mTORC2 counteracts virus-induced apoptosis, promoting the survival of infected cells. This work reveals a novel mechanism by which the dengue flavivirus can promote cell survival to maximize viral replication.

scholarly journals Megaproject Management Research: The Status Quo and Future Directions

Buildings ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 567
Author(s):  
Hongping Yuan ◽  
Wenbo Du ◽  
Zeyu Wang ◽  
Xiangnan Song
Keyword(s):  
Developed Countries ◽  
The United States ◽  
Status Quo ◽  
Current Status ◽  
Research Trend ◽  
Research Development ◽  
Management Research ◽  
Future Directions ◽  
Systematic Examination ◽  
The Status

Megaproject practices worldwide have triggered increasing research in megaproject management issues and led to an increasing number of papers being published during the last decade. However, it is demonstrated by the literature that there is no systematic examination on research development in the discipline of megaproject management, and consequently it is very difficult for scholars to quickly understand and grasp the research trend. Therefore, a research question naturally comes out, i.e., what is the status quo of megaproject management research and what are the research directions worthy of further investigation? This study aims to answer the question by conducting a systematic examination of the research development in the discipline of megaproject management. A total of 117 relevant articles, identified from six major international journals between 2009 and 2021, were analyzed based on the number of papers published annually, main author contributions, citations, categorization of the research methods and data analysis methods adopted, and research topics covered. The results indicated that developed countries, such as Australia, Canada, the United States, and the United Kingdom, have enjoyed significant advantages in terms of megaproject management research. It also revealed that more sophisticated views and theory have been used effectively, rather than only basic qualitative methods, in a number of studies on megaproject management. Future studies on megaproject management will be led globally, where megaprojects will remain designed and built to better built environments. In addition, continuous in-depth research on related topics can promote innovation in megaproject management to achieve sustainable megaproject development. Megaproject management will continue to be a hot research topic in the future; in particular, megaproject investment and finance management have emerged as new challenging topics. The findings can be valuable for both industry practitioners and researchers to gain deeper understanding of the current status and future directions of megaproject management research.

scholarly journals Transcriptional role of p53 in interferon-mediated antiviral immunity

2008 ◽  
Vol 205 (8) ◽  
pp. 1929-1938 ◽  
Author(s):  
César Muñoz-Fontela ◽  
Salvador Macip ◽  
Luis Martínez-Sobrido ◽  
Lauren Brown ◽  
Joseph Ashour ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Viral Replication ◽  
Viral Infections ◽  
Suppressor Gene ◽  
Central Component ◽  
Type I ◽  
Infected Cells

Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene.

The Status, Development and Future Role of Radiobeacon Differential GNSS

1998 ◽  
Vol 51 (2) ◽  
pp. 152-158 ◽  
Author(s):  
N. Ward
Keyword(s):  
Global Navigation Satellite Systems ◽  
Current Status ◽  
Automatic Identification ◽  
Future Role ◽  
Satellite Systems ◽  
Advantages And Disadvantages ◽  
The Status ◽  
Differential Corrections ◽  
Global Navigation Satellite

Marine radiobeacons have been used to broadcast differential corrections for global navigation satellite systems (DGNSS) for nearly a decade. The method has become the accepted international standard for maritime applications. The background to the development of the system is described and the current status of radiobeacon DGNSS services around the world reported. The applications are discussed, including the function of radiobeacon DGNSS as the position sensor within integrated systems, together with the performance requirements imposed by associated systems such as ECDIS and Automatic Identification Systems. The advantages and disadvantages of the radiobeacon system in regulatory, administrative and technical terms are discussed and the potential for development of the system is considered. The future role of radiobeacon DGNSS in the overall mix of systems is assessed taking into account the introduction of geo-stationary overlays, and possibly Loran-C, for provision of DGNSS corrections.

scholarly journals The Role of Space Observations in The Calibration of Fundamental Stellar Quantities

1985 ◽  
Vol 111 ◽  
pp. 209-224
Author(s):  
Arthur D. Code
Keyword(s):  
Current Status ◽  
Ultraviolet Spectrophotometry ◽  
Data Bases ◽  
Future Directions ◽  
Composite Systems ◽  
Early Type Stars ◽  
Stellar Properties ◽  
Ultraviolet Observations ◽  
Space Observations

This paper summarizes the current status of ultraviolet spectrophotometry with emphasis on the instrumental characteristics unique to space observations and on the application of existing data to the calibration of stellar properties. The currently available data bases will be briefly reviewed. When combined with ground based data, ultraviolet observations provide information on effective temperatures and bolometric corrections for early type stars and on the nature of the intervening interstellar medium. The ultraviolet measurements are sensitive to chemical composition differences and provide a powerful tool in discussion of stellar evolution in composite systems. This review concludes with a brief discussion of future directions in instrumentation and analysis.

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