scholarly journals Immunomodulatory Effects of Hydroxychloroquine and Chloroquine in Viral Infections and Their Potential Application in Retinal Gene Therapy

2020 ◽  
Vol 21 (14) ◽  
pp. 4972
Author(s):  
Laurel Chandler ◽  
Imran Yusuf ◽  
Michelle McClements ◽  
Alun Barnard ◽  
Robert MacLaren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Viral Infections ◽  
Adjunctive Treatment ◽  
Immunomodulatory Activity ◽  
Immunomodulatory Effects ◽  
Inflammatory Reactions ◽  
Potential Benefits ◽  
Lower Drug ◽  
High Concentrations ◽  
Retinal Gene Therapy

Effective treatment of retinal diseases with adeno-associated virus (AAV)-mediated gene therapy is highly dependent on the proportion of successfully transduced cells. However, due to inflammatory reactions at high vector doses, adjunctive treatment may be necessary to enhance the therapeutic outcome. Hydroxychloroquine and chloroquine are anti-malarial drugs that have been successfully used in the treatment of autoimmune diseases. Evidence suggests that at high concentrations, hydroxychloroquine and chloroquine can impact viral infection and replication by increasing endosomal and lysosomal pH. This effect has led to investigations into the potential benefits of these drugs in the treatment of viral infections, including human immunodeficiency virus and severe acute respiratory syndrome coronavirus-2. However, at lower concentrations, hydroxychloroquine and chloroquine appear to exert immunomodulatory effects by inhibiting nucleic acid sensors, including toll-like receptor 9 and cyclic GMP-AMP synthase. This dose-dependent effect on their mechanism of action supports observations of increased viral infections associated with lower drug doses. In this review, we explore the immunomodulatory activity of hydroxychloroquine and chloroquine, their impact on viral infections, and their potential to improve the efficacy and safety of retinal gene therapy by reducing AAV-induced immune responses. The safety and practicalities of delivering hydroxychloroquine into the retina will also be discussed.

scholarly journals C-type lectins and extracellular vesicles in virus-induced NETosis

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Pei-Shan Sung ◽  
Shie-Liang Hsieh
Keyword(s):  
Extracellular Vesicles ◽  
Viral Infections ◽  
Multiple Organ ◽  
Intercellular Adhesion Molecule ◽  
Inflammatory Reactions ◽  
Intravascular Coagulopathy ◽  
Encephalomyelitis Virus ◽  
Toll Like Receptor 2 ◽  
Lectin Family ◽  
Virus Spreading

AbstractDysregulated formation of neutrophil extracellular traps (NETs) is observed in acute viral infections. Moreover, NETs contribute to the pathogenesis of acute viral infections, including those caused by the dengue virus (DV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, excessive NET formation (NETosis) is associated with disease severity in patients suffering from SARS-CoV-2-induced multiple organ injuries. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and other members of C-type lectin family (L-SIGN, LSECtin, CLEC10A) have been reported to interact with viral glycans to facilitate virus spreading and exacerbates inflammatory reactions. Moreover, spleen tyrosine kinase (Syk)-coupled C-type lectin member 5A (CLEC5A) has been shown as the pattern recognition receptor for members of flaviviruses, and is responsible for DV-induced cytokine storm and Japanese encephalomyelitis virus (JEV)-induced neuronal inflammation. Moreover, DV activates platelets via CLEC2 to release extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs). The DV-activated EXOs (DV-EXOs) and MVs (DV-MVs) stimulate CLEC5A and Toll-like receptor 2 (TLR2), respectively, to enhance NET formation and inflammatory reactions. Thus, EVs from virus-activated platelets (PLT-EVs) are potent endogenous danger signals, and blockade of C-type lectins is a promising strategy to attenuate virus-induced NETosis and intravascular coagulopathy.

scholarly journals Gene Therapy in Hemophilia: Recent Advances

2021 ◽  
Vol 22 (14) ◽  
pp. 7647
Author(s):  
E. Carlos Rodríguez-Merchán ◽  
Juan Andres De Pablo-Moreno ◽  
Antonio Liras
Keyword(s):  
Gene Therapy ◽  
Adverse Events ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Cost Savings ◽  
Factor Ix ◽  
Clotting Factors ◽  
Advanced Therapies ◽  
Potential Benefits

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.

Physical Exercise and Yoga: as an alternative approach towards COVID-19 management

2021 ◽  
Vol 07 ◽  
Author(s):  
Saurabh Kumar ◽  
Sakshi Sudha ◽  
Madhu Chopra ◽  
Famida Khan ◽  
Kanupriya Sharma
Keyword(s):  
Physical Exercise ◽  
Literature Search ◽  
Viral Infections ◽  
Cost Effective ◽  
Mental Wellbeing ◽  
World Population ◽  
Cd8 Cells ◽  
Global Pandemic ◽  
Potential Benefits ◽  
Novel Coronavirus

Background: Novel Coronavirus (COVID-19), a highly contagious ssRNA +Ve sense virus that emerged in late 2019, has created a global panic. With no effective therapy available, the virus has significantly affected the world population causing millions of death. Therefore, it is the utmost need to look towards all the possible strategies to benefit the community. Objectives: In view of the current global pandemic, we tried to discuss the potential benefits of two cost-effective alternative approaches, i.e., physical exercise and yoga. Method: The editorial is based on a literature search available on PubMed, Google Scholar, and WHO portal. Search terminologies include “yoga”, “physical exercise”, “COVID-19”, “viral infections”, and a combination of these words. Results: A literature search defines yoga and physical exercise efficacy in different viral diseases, including HIV, influenza, and HSV. It ameliorates the quality of life (QoL) by improving both the physical and mental wellbeing of an individual. This is mainly done by promoting the better functioning of the immune system (increases CD4+ and CD8+ cells and reduces pro-inflammatory response). Conclusions: Regular involvement of these activities in day-to-day life may limit latent virus reactivations and reduce infection chances.

C3-targeted retinal gene therapy limits neurodegeneration onset and progression in age-related mouse glaucoma

2018 ◽  
Vol 102 ◽  
pp. 136
Author(s):  
Alejandra Bosco ◽  
Sarah Anderson ◽  
Kevin Breen ◽  
Cesar Romero ◽  
Michael Steele ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Age Related ◽  
Retinal Gene Therapy

Solid lipid nanoparticles for retinal gene therapy: Transfection and intracellular trafficking in RPE cells

2008 ◽  
Vol 360 (1-2) ◽  
pp. 177-183 ◽  
Author(s):  
A. del Pozo-Rodríguez ◽  
D. Delgado ◽  
M.A. Solinís ◽  
A.R. Gascón ◽  
J.L. Pedraz
Keyword(s):  
Gene Therapy ◽  
Solid Lipid Nanoparticles ◽  
Intracellular Trafficking ◽  
Lipid Nanoparticles ◽  
Rpe Cells ◽  
Solid Lipid ◽  
Retinal Gene Therapy

scholarly journals Nanoparticles for retinal gene therapy

2010 ◽  
Vol 29 (5) ◽  
pp. 376-397 ◽  
Author(s):  
Shannon M. Conley ◽  
Muna I. Naash
Keyword(s):  
Gene Therapy ◽  
Retinal Gene Therapy

scholarly journals Impact of Vital Dyes on Cell Viability and Transduction Efficiency of AAV Vectors Used in Retinal Gene Therapy Surgery: An In Vitro and In Vivo Analysis

2017 ◽  
Vol 6 (4) ◽  
pp. 4 ◽  
Author(s):  
Anna P. Salvetti ◽  
Maria I. Patrício ◽  
Alun R. Barnard ◽  
Harry O. Orlans ◽  
Doron G. Hickey ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cell Viability ◽  
Transduction Efficiency ◽  
Vital Dyes ◽  
In Vivo Analysis ◽  
Retinal Gene Therapy

scholarly journals Monocytes in Neonatal Bacterial Sepsis: Think Tank or Workhorse?

BioChem ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 27-43
Author(s):  
Caitlin Doughty ◽  
Louise Oppermann ◽  
Niels-Ulrik Hartmann ◽  
Stephan Dreschers ◽  
Christian Gille ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Bacterial Infections ◽  
Cell Activation ◽  
Viral Infections ◽  
Organ Damage ◽  
Host Responses ◽  
Critical Event ◽  
Think Tank ◽  
Inflammatory Reactions ◽  
Inflammatory Conditions

Infection and sepsis remain among the leading causes of neonatal mortality. The susceptibility of newborns to infection can be attributed to their immature immune system. Regarding immune response, monocytes represent a numerically minor population of leukocytes. However, they contribute to a variety of immunological demands, such as continuous replenishment of resident macrophages under non-infectious conditions and migration to inflamed sites where they neutralize pathogens and secrete cytokines. Further functions include the presentation of antigens and T-cell activation. Cytokines coordinate host responses to bacterial and viral infections and orchestrate ongoing physiological signaling between cells of non-immune tissues. A critical event is the skewing of the cytokine repertoire to achieve a resolution of infection. In this regard, monocytes may hold a key position as deciders in addition to their phagocytic activity, securing the extinction of pathogens to prevent broader organ damage by toxins and pro-inflammatory reactions. Neonatal monocytes undergo various regulatory and metabolic changes. Thus, they are thought to be vulnerable in anticipating pro-inflammatory conditions and cause severe progressions which increase the risk of developing sepsis. Furthermore, clinical studies have shown that exposure to inflammation puts neonates at a high risk for adverse pulmonary, immunological and other organ developments, which may result in multiorgan disease. This review discusses significant functions and impairments of neonatal monocytes that are decisive for the outcome of bacterial infections.

Sign in / Sign up

Export Citation Format

Share Document