Effects of ammonia exposure on apoptosis, oxidative stress and immune response in pufferfish (Takifugu obscurus)

The DNA damage response and repair (DDR/R) network, a sum of hierarchically structured signaling pathways that recognize and repair DNA damage, and the immune response to endogenous and/or exogenous threats, act synergistically to enhance cellular defense. On the other hand, a deregulated interplay between these systems underlines inflammatory diseases including malignancies and chronic systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Patients with these diseases are characterized by aberrant immune response to self-antigens with widespread production of autoantibodies and multiple-tissue injury, as well as by the presence of increased oxidative stress. Recent data demonstrate accumulation of endogenous DNA damage in peripheral blood mononuclear cells from these patients, which is related to (a) augmented DNA damage formation, at least partly due to the induction of oxidative stress, and (b) epigenetically regulated functional abnormalities of fundamental DNA repair mechanisms. Because endogenous DNA damage accumulation has serious consequences for cellular health, including genomic instability and enhancement of an aberrant immune response, these results can be exploited for understanding pathogenesis and progression of systemic autoimmune diseases, as well as for the development of new treatments.

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Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

10.1101/2020.03.30.20047852 ◽

2020 ◽

Cited By ~ 3

Author(s):

Amr H. Sawalha ◽

Ming Zhao ◽

Patrick Coit ◽

Qianjin Lu

Keyword(s):

Oxidative Stress ◽

Immune Response ◽

Viral Entry ◽

Viral Infections ◽

Severe Disease ◽

Disease Course ◽

Vicious Cycle ◽

Respiratory Complications ◽

Disease Remission ◽

Functional Receptor

SummaryInfection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.

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THE BIOLOGICAL SIGNIFICANCE OF SELENIUM AND ITS PLACE IN RNA VIRAL DISEASES

Trace Elements in Medicine (Moscow) ◽

10.19112/2413-6174-2020-21-4-21-31 ◽

2020 ◽

Vol 21 (4) ◽

pp. 21-31

Author(s):

T.M. Guseynov ◽

◽

R.T. Guliyeva ◽

F.R. Yakhyayeva ◽

◽

...

Keyword(s):

Oxidative Stress ◽

Immune Response ◽

Viral Infections ◽

Biological Significance ◽

The Body ◽

Viral Diseases ◽

Essential Trace Element ◽

Regulatory Processes ◽

P Protein ◽

Almost All

ABSTRACT. Selenium as an essential trace element takes part in the regulation of many vital processes. This is realized with the help of over 25 selenoproteins that affect oxidative stress, immune response, hormonal metabolism, cognitive function, etc. Recently (in the next 30 - 40 years), there have been reports of the effect on viral infections, which have now become widespread. It turned out that almost all RNA viruses are selenium-dependent objects, that is, their genome contains the codes of the most important selenium containing proteins, including such as glutathione peroxidase, thioredoxinreductase, selenium-P protein, etc. Their synthesis during the development of a viral infection at the expense of the host leads to a weakening of the synthesis of the body's own intracellular selenium proteins, which contributes to the development of oxidative stress and a failure of the immune response. And this leads to the devastation of the selenium depot of the body, intended for the synthesis of its selenium proteins, which participate in vital regulatory processes. This circumstance determines, to replenish the body's resources with selenium, the expediency of using selenium-containing pharmacopoeia preparations as adjuvant in the treatment of RNA viral infections.

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Therapeutic Effect of Camel Milk and Its Exosomes on MCF7 Cells In Vitro and In Vivo

Integrative Cancer Therapies ◽

10.1177/1534735418786000 ◽

2018 ◽

Vol 17 (4) ◽

pp. 1235-1246 ◽

Cited By ~ 27

Author(s):

Abdelnaser A. Badawy ◽

Mohammed A. El-Magd ◽

Sana A. AlSadrah

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Immune Response ◽

Local Injection ◽

Camel Milk ◽

Anticancer Effect ◽

Mcf7 Cells ◽

Beneficial Effects

Background/Objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action. Methods/Results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by ( a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), ( b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); ( c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), ( d) notable reduction in expression of inflammation-( IL1b, NFκB), angiogenesis-( VEGF) and metastasis-( MMP9, ICAM1) related genes; and ( e) higher immune response (high number of CD+4, CD+8, NK1.1 T cells in spleen). Conclusions: Overall, administration of camel milk–derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.

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Neuroinflammation in Primary Open-Angle Glaucoma

Journal of Clinical Medicine ◽

10.3390/jcm9103172 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3172 ◽

Cited By ~ 1

Author(s):

Stefania Vernazza ◽

Sara Tirendi ◽

Anna Maria Bassi ◽

Carlo Enrico Traverso ◽

Sergio Claudio Saccà

Keyword(s):

Oxidative Stress ◽

Immune Response ◽

Trabecular Meshwork ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Glaucoma Surgery ◽

Open Angle ◽

Antioxidant Defences ◽

Age Related ◽

Wide Range

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increasing evidence suggests oxidative damage and immune response defects are key factors contributing to glaucoma onset. Indeed, both the failure of the trabecular meshwork tissue in the conventional outflow pathway and the neuroinflammation process, which drives the neurodegeneration, seem to be linked to the age-related over-production of free radicals (i.e., mitochondrial dysfunction) and to oxidative stress-linked immunostimulatory signaling. Several previous studies have described a wide range of oxidative stress-related makers which are found in glaucomatous patients, including low levels of antioxidant defences, dysfunction/activation of glial cells, the activation of the NF-κB pathway and the up-regulation of pro-inflammatory cytokines, and so on. However, the intraocular pressure is still currently the only risk factor modifiable by medication or glaucoma surgery. This present review aims to summarize the multiple cellular processes, which promote different risk factors in glaucoma including aging, oxidative stress, trabecular meshwork defects, glial activation response, neurodegenerative insults, and the altered regulation of immune response.

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