The Role of Exosomes in the Treatment, Prevention, Diagnosis, and Pathogenesis of COVID-19

2021 ◽  
Author(s):  
Elke Zani-Ruttenstock ◽  
Lina Antounians ◽  
Kasra Khalaj ◽  
Rebeca L. Figueira ◽  
Augusto Zani
Keyword(s):  
Treatment Strategies ◽  
Lessons Learned ◽  
Health Concern ◽  
Plasma Therapy ◽  
The Status ◽  
Low Toxicity ◽  
Novel Treatment Strategies ◽  
Novel Coronavirus ◽  
Clinical Conditions

AbstractThe novel coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), continues to be a major health concern. In search for novel treatment strategies against COVID-19, exosomes have attracted the attention of scientists and pharmaceutical companies worldwide. Exosomes are small extracellular vesicles, secreted by all types of cells, and considered as key mediators of intercellular communication and stem-cell paracrine signaling. Herein, we reviewed the most recent literature about the role of exosomes as potential agents for treatment, prevention, diagnosis, and pathogenesis of COVID-19. Several studies and ongoing clinical trials have been investigating the anti-inflammatory, immunomodulatory, and reparative effects of exosomes derived from mesenchymal stem/stromal cells for COVID-19-related acute lung injury. Other studies reported that exosomes play a key role in convalescent plasma therapy for COVID-19, and that they could be of use for the treatment of COVID-19 Kawasaki's-like multisystem inflammatory syndrome and as drug delivery nanocarriers for antiviral therapy. Harnessing some advantageous aspects of exosome biology, such as their endogenous origin, capability of crossing biological barriers, high stability in circulation, and low toxicity and immunogenicity, several companies have been testing exosome-based vaccines against SARS-CoV-2. As they carry cargos that mimic the status of parent cells, exosomes can be isolated from a variety of sources, including plasma, and employed as biomarkers of COVID-19. Lastly, there is growing evidence supporting the role of exosomes in COVID-19 infection, spread, reactivation, and reinfection. The lessons learned using exosomes for COVID-19 will help determine their efficacy and applicability in other clinical conditions.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

Unfinished Business

2018 ◽  
pp. 213-236
Author(s):  
Natalie G. Adams ◽  
James H. Adams
Keyword(s):  
Cultural Change ◽  
School Desegregation ◽  
Lessons Learned ◽  
Black Parents ◽  
Unfinished Business ◽  
Student Government ◽  
Informal Curriculum ◽  
The Status ◽  
Different Parts

This concluding chapter summarizes the lessons learned from studying the stories of school desegregation in Mississippi. In organizing the book with separate chapters on black parents, superintendents, principals, and teachers, this study hoped to capture the nuances of how school desegregation was accomplished, fought for, resisted, and doomed in differing ways in different parts of the state. The inclusion of the role of sports, band, the prom, cheerleading, and student government during the school desegregation process is a reminder that educational reformers cannot ignore the importance of the informal curriculum, the hidden curriculum, and the extracurricular of schools. Meanwhile, the chapters on protests and private schools illustrate two primary ways in which people responded to this monumental cultural change that threatened the status quo: they resisted in various ways through conventional methods of protest, and they formed a countermovement that sought to retain the tribalism to which they clung and around which their identities were built.

scholarly journals Mitochondria: Potential Targets for Osteoarthritis

2020 ◽  
Vol 7 ◽  
Author(s):  
Xingjia Mao ◽  
Panfeng Fu ◽  
Linlin Wang ◽  
Chuan Xiang
Keyword(s):  
Mitochondrial Function ◽  
Treatment Strategies ◽  
Cartilage Regeneration ◽  
Cartilage Degeneration ◽  
Research Field ◽  
Mitochondrial Dysfunctions ◽  
Joint Disorder ◽  
Global Status ◽  
Novel Treatment Strategies

Osteoarthritis (OA) is a common and disabling joint disorder that is mainly characterized by cartilage degeneration and narrow joint spaces. The role of mitochondrial dysfunction in promoting the development of OA has gained much attention. Targeting endogenous molecules to improve mitochondrial function is a potential treatment for OA. Moreover, research on exogenous drugs to improve mitochondrial function in OA based on endogenous molecular targets has been accomplished. In addition, stem cells and exosomes have been deeply researched in the context of cartilage regeneration, and these factors both reverse mitochondrial dysfunctions. Thus, we hypothesize that biomedical approaches will be applied to the treatment of OA. Furthermore, we have summarized the global status of mitochondria and osteoarthritis research in the past two decades, which will contribute to the research field and the development of novel treatment strategies for OA.

scholarly journals A Review of Key Biological and Molecular Events Underpinning Transformation of Melanocytes to Primary and Metastatic Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2041 ◽  
Author(s):  
Louise A. Jackett ◽  
Richard A. Scolyer
Keyword(s):  
Treatment Strategies ◽  
Genomic Analysis ◽  
Molecular Therapy ◽  
Health Concern ◽  
Targeted Molecular Therapy ◽  
Public Health Concern ◽  
Molecular Events ◽  
Key Events ◽  
Potential Tool

Melanoma is a major public health concern that is responsible for significant morbidity and mortality, particularly in countries such as New Zealand and Australia where it is the commonest cause of cancer death in young adults. Until recently, there were no effective drug therapies for patients with advanced melanoma however significant advances in our understanding of the biological and molecular basis of melanoma in recent decades have led to the development of revolutionary treatments, including targeted molecular therapy and immunotherapy. This review summarizes our current understanding of the key events in the pathway of melanomagenesis and discusses the role of genomic analysis as a potential tool for improved diagnostic evaluation, prognostication and treatment strategies. Ultimately, it is hoped that a continued deeper understanding of the mechanisms of melanomagenesis will lead to the development of even more effective treatments that continue to provide better outcomes for patients with melanoma.

scholarly journals High Inter- and Intratumoral Variability of Ki67 Labeling Index in Newly Diagnosed Prostate Cancer with High Gleason Scores

Pathobiology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Tatjana Vlajnic ◽  
Patrik Brunner ◽  
Serenella Eppenberger-Castori ◽  
Cyrill A. Rentsch ◽  
Tobias Zellweger ◽  
...  
Keyword(s):  
Gleason Score ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Labeling Index ◽  
High Grade ◽  
Newly Diagnosed ◽  
Ki67 Labeling Index ◽  
The Status ◽  
Underlying Mechanisms

<b><i>Background:</i></b> The majority of studies investigating the role of Ki67 labeling index (LI) in prostate carcinoma (PC) focused on localized PC treated radically, where Ki67 LI is regarded as a prognostic marker. The relevance of Ki67 in advanced PC remains largely unexplored. While Gleason score is still one of the best indicators of clinical outcomes in PC, differences in progression-free survival and overall survival in patients with high Gleason scores suggest that additional factors are involved in tumor progression. Understanding the underlying mechanisms could help to optimize treatment strategies for an individual patient. Here, we aimed to determine the inter- and intratumoral distribution of Ki67 LI in patients with PC with high Gleason scores and to correlate Ki67 LI with the status of ERG, PTEN, and Bcl-2. <b><i>Methods:</i></b> Immunohistochemistry for Ki67, ERG, PTEN, and Bcl-2 was performed on core needle biopsies from 112 patients with newly diagnosed PC Gleason score 8, 9, and 10. <b><i>Results:</i></b> Using a cutoff of ≥10%, 17/112 cases (15%) had a homogeneously low and 95/112 cases (85%) a high Ki67 LI. 41% of cases showed intratumoral heterogeneity containing areas with low and high proliferation. There was no association between Ki67 LI and ERG, PTEN, or Bcl-2 status. <b><i>Conclusions:</i></b> Our data demonstrate major inter- and intratumoral variability of Ki67 LI in high-grade PC with a surprisingly low Ki67 LI in a subset of cases. Further studies are necessary to explore the molecular basis and potential clinical implications of a paradoxically low proliferation rate in high-grade PC.

scholarly journals Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints

2021 ◽  
Vol 8 ◽  
Author(s):  
Janne W. Bolt ◽  
Chaja M. J. van Ansenwoude ◽  
Ihsan Hammoura ◽  
Marleen G. van de Sande ◽  
Lisa G. M. van Baarsen
Keyword(s):  
Psoriatic Arthritis ◽  
Translational Research ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Treatment Strategies ◽  
Continuous Treatment ◽  
Adaptive Immune Cells ◽  
Novel Treatment Strategies

Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, remission of disease is not achieved in a considerable group of patients, continuous treatment is very often required to reach clinical remission, and prevention of PsA in patients with psoriasis (PsO) is currently impossible. A better understanding of PsA pathogenesis is required to develop novel treatment strategies that target inflammation and destruction more effectively and at an early stage of the disease, or even before clinically manifest disease. The skin is considered as one of the sites of onset of immune activation, triggering the inflammatory cascade in PsA. PsO develops into PsA in 30% of the PsO patients. Influenced by environmental and genetic factors, the inflammatory process in the skin, entheses, and/or gut may evolve into synovial tissue inflammation, characterized by influx of immune cells. The exact role of the innate and adaptive immune cells in disease pathogenesis is not completely known. The involvement of activated IL-17A+ T cells could implicate early immunomodulatory events generated in lymphoid organs thereby shaping the pathogenic inflammatory response leading to disease. In this perspective article, we provide the reader with an overview of the current literature regarding the immunological changes observed during the earliest stages of PsA. Moreover, we will postulate future areas of translational research aimed at increasing our knowledge on the molecular mechanisms driving disease development, which will aid the identification of novel potential therapeutic targets to limit the progression of PsA.

scholarly journals Protein kinase J regulates Rv0642c expression and sensitivity to rifampicin of mycobacteria

2021 ◽  
Author(s):  
Kishore Kumar Srivastava ◽  
Diwakar Kumar Singh ◽  
Sameer Tiwari ◽  
Kumari Kripalata
Keyword(s):  
Rational Design ◽  
Treatment Strategies ◽  
Host Immune System ◽  
Intracellular Growth ◽  
Methyltransferase Activity ◽  
Knock Out ◽  
Long Duration ◽  
Highly Sensitive ◽  
Novel Treatment Strategies

Mycobacterium tuberculosis (M.tb) persists for long-duration inside the human host in both active and latent form by modulating the immune response. The mechanisms employed by M.tb to survive inside the host and evade the host immune system need to be explored in greater depth for the rational design of novel treatment strategies. The phosphorylation and methylation of biomolecules need to be addressed in mycobacteria because it has an important role in infection establishment and persistence. In the present study, we elaborate on the role of PknJ in the slow growth of BCG and its association with mmaA4 protein during extracellular and intracellular growth. The pknJ knock-out (KO) BCG has been used to decode the functional significance in mycobacteria. The mmaA4 expression and methyltransferase activity is decreased in knocked-out BCG strain (pknJ-/-) during extracellular growth, while mmaA4 expression and methyltransferase activity is increased during intracellular growth of mycobacteria. The knocked-out BCG strain is highly sensitive to the rifampicin antibiotics during extracellular growth in compared to control. A significant association of pknJ and mmaA4 was found in our studies during the growth and intracellular persistence of mycobacteria.

scholarly journals Severity of Coronavirus Disease 2019 in Patients with Cancer

2020 ◽  
Vol 4 (2) ◽  
pp. 119-126
Author(s):  
Zahraa Qusairy ◽  
Miran Rada
Keyword(s):  
Global Health ◽  
Treatment Options ◽  
Underlying Disease ◽  
Therapeutic Agents ◽  
The Novel ◽  
Supportive Treatment ◽  
Plasma Therapy ◽  
Patients With Cancer ◽  
Novel Coronavirus

The outbreak of the novel coronavirus disease 2019 (COVID-19) has appeared to be one of the biggest global health threats worldwide with no specific therapeutic agents. As of August 2020, over 22.4 million confirmed cases and more than 788,000 deaths have been reported globally, and the toll is expected to increase before the pandemic is over. Given the aggressive nature of their underlying disease, cancer patients seem to be more vulnerable to COVID-19 and various studies have confirmed this hypothesis. Herein, we review the current information regarding the role of cancer in SARS-CoV-2 infections. Moreover, we discuss the effective supportive treatment options for COVID-19 including Dexamethasone, Tocilizumab and Remdesivir and convalescent plasma therapy (CPT), as well as discuss their efficacy in COVID-19 patients with cancer.

Mucosal Dendritic Cell Subsets Control HIV-1’s Viral Fitness

2020 ◽  
Vol 7 (1) ◽  
pp. 385-402
Author(s):  
Bernadien M. Nijmeijer ◽  
Catharina J.M. Langedijk ◽  
Teunis B.H. Geijtenbeek
Keyword(s):  
Dendritic Cell ◽  
Sexual Transmission ◽  
Treatment Strategies ◽  
Viral Fitness ◽  
Immunodeficiency Virus ◽  
Novel Treatment Strategies ◽  
Hiv 1 ◽  
Selection Of

Dendritic cell (DC) subsets are abundantly present in genital and intestinal mucosal tissue and are among the first innate immune cells that encounter human immunodeficiency virus type 1 (HIV-1) after sexual contact. Although DCs have specific characteristics that greatly enhance HIV-1 transmission, it is becoming evident that most DC subsets also have virus restriction mechanisms that exert selective pressure on the viruses during sexual transmission. In this review we discuss the current concepts of the immediate events following viral exposure at genital mucosal sites that lead to selection of specific HIV-1 variants called transmitted founder (TF) viruses. We highlight the importance of the TF HIV-1 phenotype and the role of different DC subsets in establishing infection. Understanding the biology of HIV-1 transmission will contribute to the design of novel treatment strategies preventing HIV-1 dissemination.

scholarly journals Challenging a Misnomer? The Role of Inflammatory Pathways in Inflammatory Breast Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Riley J. Morrow ◽  
Nima Etemadi ◽  
Belinda Yeo ◽  
Matthias Ernst
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Molecular Evidence ◽  
Her2 Positive ◽  
Extrinsic Factors ◽  
Cancer Subtypes ◽  
Novel Treatment Strategies

Inflammatory breast cancer is a rare, yet highly aggressive form of breast cancer, which accounts for less than 5% of all locally advanced presentations. The clinical presentation of inflammatory breast cancer often differs significantly from that of noninflammatory breast cancer; however, immunohistochemistry reveals few, if any, distinguishing features. The more aggressive triple-negative and HER2-positive breast cancer subtypes are overrepresented in inflammatory breast cancer compared with noninflammatory breast cancer, with a poorer prognosis in response to conventional therapies. Despite its name, there remains some controversy regarding the role of inflammation in inflammatory breast cancer. This review summarises the current molecular evidence suggesting that inflammatory signaling pathways are upregulated in this disease, including NF-κB activation and excessive IL-6 production among others, which may provide an avenue for novel therapeutics. The role of the tumor microenvironment, through tumor-associated macrophages, infiltrating lymphocytes, and cancer stem cells is also discussed, suggesting that these tumor extrinsic factors may help account for the differences in behavior between inflammatory breast cancer and noninflammatory breast cancer. While there are various novel treatment strategies already underway in clinical trials, the need for further development of preclinical models of this rare but aggressive disease is paramount.

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