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1.
Can J Urol ; 29(4): 11224-11230, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1989837

ABSTRACT

Prostate-specific antigen (PSA) screening remains the mainstay for early detection of prostate cancer. Although PSA is a nonspecific prostate cancer biomarker, its specificity for high grade prostate cancer can be enhanced by pre-biopsy liquid biomarkers including the Exosome Dx Prostate IntelliScore (EPI) test. EPI is a stand-alone urine genomic test that measures 3 exosome-derived gene expression signatures without the need for digital rectal examination (DRE) or inclusion of standard of care parameters in the test algorithm. EPI has broad clinical utility as a risk stratification tool for clinically significant high grade prostate cancer in men considering diagnostic prostate biopsy (MRI-targeted and systematic biopsy). During the COVID-19 pandemic, the EPI At-Home Collection Kit was introduced and quickly became an important component of tele-urology. The EPI test has emerged as a prioritization tool for primary care referral to urologists and for prostate biopsy scheduling. EPI provides an objective and actionable genomic risk assessment tool for high grade prostate cancer and is a critical part of the informed decision-making regarding biopsy (targeted, systematic or both) in both urology and primary care practices.


Subject(s)
COVID-19 , Exosomes , Prostatic Neoplasms , Urology , Biomarkers, Tumor/genetics , Biopsy , COVID-19/diagnosis , COVID-19 Testing , Exosomes/genetics , Exosomes/pathology , Humans , Male , Pandemics , Primary Health Care , Prostate/pathology , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology
2.
Cardiovasc Res ; 117(10): 2161-2174, 2021 08 29.
Article in English | MEDLINE | ID: covidwho-1266111

ABSTRACT

We review some of the important discoveries and advances made in basic and translational cardiac research in 2020. For example, in the field of myocardial infarction (MI), new aspects of autophagy and the importance of eosinophils were described. Novel approaches, such as a glycocalyx mimetic, were used to improve cardiac recovery following MI. The strategy of 3D bio-printing was shown to allow the fabrication of a chambered cardiac organoid. The benefit of combining tissue engineering with paracrine therapy to heal injured myocardium is discussed. We highlight the importance of cell-to-cell communication, in particular, the relevance of extracellular vesicles, such as exosomes, which transport proteins, lipids, non-coding RNAs, and mRNAs and actively contribute to angiogenesis and myocardial regeneration. In this rapidly growing field, new strategies were developed to stimulate the release of reparative exosomes in ischaemic myocardium. Single-cell sequencing technology is causing a revolution in the study of transcriptional expression at cellular resolution, revealing unanticipated heterogeneity within cardiomyocytes, pericytes and fibroblasts, and revealing a unique subpopulation of cardiac fibroblasts. Several studies demonstrated that exosome- and non-coding RNA-mediated approaches can enhance human induced pluripotent stem cell (iPSC) viability and differentiation into mature cardiomyocytes. Important details of the mitochondrial Ca2+ uniporter and its relevance were elucidated. Novel aspects of cancer therapeutic-induced cardiotoxicity were described, such as the novel circular RNA circITCH, which may lead to novel treatments. Finally, we provide some insights into the effects of SARS-CoV-2 on the heart.


Subject(s)
Biomedical Research , Cardiology , Cell Proliferation , Heart Failure/pathology , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/pathology , Regeneration , Animals , COVID-19/pathology , COVID-19/virology , Cell Communication , Cellular Microenvironment , Exosomes/metabolism , Exosomes/pathology , Heart Failure/metabolism , Heart Failure/physiopathology , Humans , Mitochondria, Heart/metabolism , Mitochondria, Heart/pathology , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/virology , Phenotype , RNA, Untranslated/metabolism , SARS-CoV-2/pathogenicity
3.
Front Immunol ; 12: 656700, 2021.
Article in English | MEDLINE | ID: covidwho-1211815

ABSTRACT

SARS-CoV-2, the novel coronavirus infection has consistently shown an association with neurological anomalies in patients, in addition to its usual respiratory distress syndrome. Multi-organ dysfunctions including neurological sequelae during COVID-19 persist even after declining viral load. We propose that SARS-CoV-2 gene product, Spike, is able to modify the host exosomal cargo, which gets transported to distant uninfected tissues and organs and can initiate a catastrophic immune cascade within Central Nervous System (CNS). SARS-CoV-2 Spike transfected cells release a significant amount of exosomes loaded with microRNAs such as miR-148a and miR-590. microRNAs gets internalized by human microglia and suppress target gene expression of USP33 (Ubiquitin Specific peptidase 33) and downstream IRF9 levels. Cellular levels of USP33 regulate the turnover time of IRF9 via deubiquitylation. Our results also demonstrate that absorption of modified exosomes effectively regulate the major pro-inflammatory gene expression profile of TNFα, NF-κB and IFN-ß. These results uncover a bystander pathway of SARS-CoV-2 mediated CNS damage through hyperactivation of human microglia. Our results also attempt to explain the extra-pulmonary dysfunctions observed in COVID-19 cases when active replication of virus is not supported. Since Spike gene and mRNAs have been extensively picked up for vaccine development; the knowledge of host immune response against spike gene and protein holds a great significance. Our study therefore provides novel and relevant insights regarding the impact of Spike gene on shuttling of host microRNAs via exosomes to trigger the neuroinflammation.


Subject(s)
COVID-19/metabolism , Exosomes/metabolism , Interferon-Stimulated Gene Factor 3, gamma Subunit/metabolism , MicroRNAs/metabolism , Microglia/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Ubiquitin Thiolesterase/metabolism , COVID-19/genetics , COVID-19/physiopathology , COVID-19/virology , Cell Line , Central Nervous System/immunology , Central Nervous System/physiopathology , Central Nervous System/virology , Endopeptidases/metabolism , Exosomes/genetics , Exosomes/pathology , Humans , Inflammation/immunology , Inflammation/virology , Interferon-beta/metabolism , MicroRNAs/genetics , Microglia/pathology , NF-kappa B/metabolism , Protein Stability , Tumor Necrosis Factor-alpha/metabolism
4.
J Cell Physiol ; 236(5): 3366-3382, 2021 05.
Article in English | MEDLINE | ID: covidwho-1107657

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has reached a pandemic level, spreading across the globe by affecting over 33 million people and causing over 1,009,270 deaths. SARS-CoV-2 is highly infectious with a high basic reproduction number (R0 ) of 2.2-5.7 that has led to its exponential spread. Besides, very little is known about it in terms of immunogenicity and its molecular targets. SARS-CoV-2 causes acute respiratory distress syndrome, followed by multiple organ failure and death in a small percentage of individuals. Cardiac injury has emerged as another dreaded outcome of COVID-19 complications. However, a thorough understanding of the pathogenesis of SARS-CoV-2 is lacking. In this review, we discuss the virus, possible mechanisms of COVID-19-induced cardiac injury, and potential therapeutic strategies, and we explore if exosomes could be targeted to treat symptoms of COVID-19. Furthermore, we discussed the virus-induced sepsis, which may be the cause of multiple organ failure, including myocardial injury.


Subject(s)
COVID-19 , Cardiovascular Diseases/etiology , Exosomes/pathology , SARS-CoV-2/pathogenicity , Sepsis/virology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , Cardiovascular Diseases/virology , Humans
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