Oxidative Stress in Malarial Diseases: Plasmodium-Human Host Interactions and Therapeutic Interventions

Hydrogen sulfide (H2S) is an essential gaseous signaling molecule. Research on its role in physiological and pathophysiological processes has greatly expanded. Endogenous enzymatic production through the transsulfuration and cysteine catabolism pathways can occur in the kidneys and blood vessels. Furthermore, non-enzymatic pathways are present throughout the body. In the renal and cardiovascular system, H2S plays an important role in maintaining the redox status at safe levels by promoting scavenging of reactive oxygen species (ROS). H2S also modifies cysteine residues on key signaling molecules such as keap1/Nrf2, NFκB, and HIF-1α, thereby promoting anti-oxidant mechanisms. Depletion of H2S is implicated in many age-related and cardiorenal diseases, all having oxidative stress as a major contributor. Current research suggests potential for H2S-based therapies, however, therapeutic interventions have been limited to studies in animal models. Beyond H2S use as direct treatment, it could improve procedures such as transplantation, stem cell therapy, and the safety and efficacy of drugs including NSAIDs and ACE inhibitors. All in all, H2S is a prime subject for further research with potential for clinical use.

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Investigating Influenza A Virus Infection: Tools To Track Infection and Limit Tropism: TABLE 1

Journal of Virology ◽

10.1128/jvi.00462-15 ◽

2015 ◽

Vol 89 (12) ◽

pp. 6167-6170 ◽

Cited By ~ 19

Author(s):

Jessica K. Fiege ◽

Ryan A. Langlois

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Therapeutic Interventions ◽

Microrna Target ◽

Influenza A Viruses ◽

Host Interactions ◽

Target Sites ◽

Recent Developments ◽

Cellular Tropism ◽

The Relationship

Influenza A viruses display a broad cellular tropism within the respiratory tracts of mammalian hosts. Uncovering the relationship between tropism and virus immunity, pathogenesis, and transmission will be critical for the development of therapeutic interventions. Here we discuss recent developments of several recombinant strains of influenza A virus. These viruses have inserted reporters to track tropism, microRNA target sites to restrict tropism, or barcodes to assess transmission dynamics, expanding our understanding of pathogen-host interactions.

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Detection of A-to-I RNA Editing in SARS-COV-2

Genes ◽

10.3390/genes13010041 ◽

2021 ◽

Vol 13 (1) ◽

pp. 41

Author(s):

Ernesto Picardi ◽

Luigi Mansi ◽

Graziano Pesole

Keyword(s):

Rna Editing ◽

Time Course ◽

Vero Cells ◽

Innate Immune ◽

Therapeutic Interventions ◽

Clinical Samples ◽

Transcriptome Data ◽

Host Interactions ◽

Rnaseq Data ◽

The Impact

ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions, and are (in the majority of cases) nonsynonymous. The impact of RNA editing on virus–host interactions could be relevant to identify potential targets for therapeutic interventions.

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Circulating Leukocytes and Oxidative Stress in Cardiovascular Diseases: A State of the Art

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2650429 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Speranza Rubattu ◽

Maurizio Forte ◽

Salvatore Raffa

Keyword(s):

Oxidative Stress ◽

Cardiovascular Diseases ◽

Stress Level ◽

Mononuclear Cells ◽

Pathological Condition ◽

Clinical Manifestations ◽

Therapeutic Interventions ◽

Oxidative Stress Level ◽

The Impact

Increased oxidative stress from both mitochondrial and cytosolic sources contributes to the development and the progression of cardiovascular diseases (CVDs), and it is a target of therapeutic interventions. The numerous efforts made over the last decades in order to develop tools able to monitor the oxidative stress level in patients affected by CVDs rely on the need to gain information on the disease state. However, this goal has not been satisfactorily accomplished until now. Among others, the isolation of circulating leukocytes to measure their oxidant level offers a valid, noninvasive challenge that has been tested in few pathological contexts, including hypertension, atherosclerosis and its clinical manifestations, and heart failure. Since leukocytes circulate in the blood stream, it is expected that they might reflect quite closely both systemic and cardiovascular oxidative stress and provide useful information on the pathological condition. The results of the studies discussed in the present review article are promising. They highlight the importance of measuring oxidative stress level in circulating mononuclear cells in different CVDs with a consistent correlation between degree of oxidative stress and severity of CVD and of its complications. Importantly, they also point to a double role of leukocytes, both as a marker of disease condition and as a direct contributor to disease progression. Finally, they show that the oxidative stress level of leukocytes reflects the impact of therapeutic interventions. It is likely that the isolation of leukocytes and the measurement of oxidative stress, once adequately developed, may represent an eligible tool for both research and clinical purposes to monitor the role of oxidative stress on the promotion and progression of CVDs, as well as the impact of therapies.

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Extracellular Vesicles in Smoking-Mediated HIV Pathogenesis and their Potential Role in Biomarker Discovery and Therapeutic Interventions

Cells ◽

10.3390/cells9040864 ◽

2020 ◽

Vol 9 (4) ◽

pp. 864 ◽

Cited By ~ 3

Author(s):

Sanjana Haque ◽

Sunitha Kodidela ◽

Kelli Gerth ◽

Elham Hatami ◽

Neha Verma ◽

...

Keyword(s):

Oxidative Stress ◽

Extracellular Vesicles ◽

Biomarker Discovery ◽

Poor Quality ◽

Therapeutic Interventions ◽

People Living With Hiv ◽

Hiv Replication ◽

Hiv Pathogenesis ◽

Potential Applications ◽

Underlying Mechanisms

In the last two decades, the mortality rate in people living with HIV/AIDS (PLWHA) has decreased significantly, resulting in an almost normal longevity in this population. However, a large portion of this population still endures a poor quality of life, mostly due to an increased inclination for substance abuse, including tobacco smoking. The prevalence of smoking in PLWHA is consistently higher than in HIV negative persons. A predisposition to cigarette smoking in the setting of HIV potentially leads to exacerbated HIV replication and a higher risk for developing neurocognitive and other CNS disorders. Oxidative stress and inflammation have been identified as mechanistic pathways in smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. Extracellular vesicles (EVs), packaged with oxidative stress and inflammatory agents, show promise in understanding the underlying mechanisms of smoking-induced HIV pathogenesis via cell-cell interactions. This review focuses on recent advances in the field of EVs with an emphasis on smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. This review also provides an overview of the potential applications of EVs in developing novel therapeutic carriers for the treatment of HIV-infected individuals who smoke, and in the discovery of novel biomarkers that are associated with HIV-smoking interactions in the CNS.

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Natural Antioxidant Anthocyanins—A Hidden Therapeutic Candidate in Metabolic Disorders with Major Focus in Neurodegeneration

Nutrients ◽

10.3390/nu11061195 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1195 ◽

Cited By ~ 28

Author(s):

Rahat Ullah ◽

Mehtab Khan ◽

Shahid Ali Shah ◽

Kamran Saeed ◽

Myeong Ok Kim

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Neurodegenerative Diseases ◽

Metabolic Disorders ◽

Antioxidant Defense System ◽

Vital Role ◽

Therapeutic Interventions ◽

Substantial Contribution ◽

Future Research ◽

Commercial Sources

All over the world, metabolic syndrome constitutes severe health problems. Multiple factors have been reported in the pathogenesis of metabolic syndrome. Metabolic disorders result in reactive oxygen species (ROS) induced oxidative stress, playing a vital role in the development and pathogenesis of major health issues, including neurological disorders Alzheimer’s disease (AD) Parkinson’s disease (PD). Considerable increasing evidence indicates the substantial contribution of ROS-induced oxidative stress in neurodegenerative diseases. An imbalanced metabolism results in a defective antioxidant defense system, free radicals causing inflammation, cellular apoptosis, and tissue damage. Due to the annual increase in financial and social burdens, in addition to the adverse effects associated with available synthetic agents, treatment diversion from synthetic to natural approaches has occurred. Antioxidants are now being considered as convincing therapeutic agents against various neurodegenerative disorders. Therefore, medicinal herbs and fruits currently receive substantially more attention as commercial sources of antioxidants. In this review, we argue that ROS-targeted therapeutic interventions with naturally occurring antioxidant flavonoid, anthocyanin, and anthocyanin-loaded nanoparticles might be the ultimate treatment against devastating illnesses. Furthermore, we elucidate the hidden potential of the neuroprotective role of anthocyanins and anthocyanin-loaded nanoparticles in AD and PD neuropathies, which lack sufficient attention compared with other polyphenols, despite their strong antioxidant potential. Moreover, we address the need for future research studies of native anthocyanins and nano-based-anthocyanins, which will be helpful in developing anthocyanin treatments as therapeutic mitochondrial antioxidant drug-like regimens to delay or prevent the progression of neurodegenerative diseases, such as AD and PD.

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Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

Seminars in Dialysis ◽

10.1111/sdi.12745 ◽

2018 ◽

Vol 32 (1) ◽

pp. 58-71 ◽

Cited By ~ 29

Author(s):

Vassilios Liakopoulos ◽

Stefanos Roumeliotis ◽

Sotirios Zarogiannis ◽

Theodoros Eleftheriadis ◽

Peter R. Mertens

Keyword(s):

Oxidative Stress ◽

Therapeutic Interventions ◽

Clinical Implications

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Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility

Antioxidants ◽

10.3390/antiox9020134 ◽

2020 ◽

Vol 9 (2) ◽

pp. 134 ◽

Cited By ~ 10

Author(s):

Karolina Nowicka-Bauer ◽

Brett Nixon

Keyword(s):

Oxidative Stress ◽

Sperm Motility ◽

Reproductive Tract ◽

Therapeutic Interventions ◽

Antioxidant Defenses ◽

Ros Production ◽

Paternal Genome ◽

Male Reproductive Tract ◽

Ability To Act ◽

The Impact

A state of oxidative stress (OS) and the presence of reactive oxygen species (ROS) in the male reproductive tract are strongly correlated with infertility. While physiological levels of ROS are necessary for normal sperm functioning, elevated ROS production can overwhelm the cell’s limited antioxidant defenses leading to dysfunction and loss of fertilizing potential. Among the deleterious pleiotropic impacts arising from OS, sperm motility appears to be particularly vulnerable. Here, we present a mechanistic account for how OS contributes to altered sperm motility profiles. In our model, it is suggested that the abundant polyunsaturated fatty acids (PUFAs) residing in the sperm membrane serve to sensitize the male germ cell to ROS attack by virtue of their ability to act as substrates for lipid peroxidation (LPO) cascades. Upon initiation, LPO leads to dramatic remodeling of the composition and biophysical properties of sperm membranes and, in the case of the mitochondria, this manifests in a dissipation of membrane potential, electron leakage, increased ROS production and reduced capacity for energy production. This situation is exacerbated by the production of cytotoxic LPO byproducts such as 4-hydroxynonenal, which dysregulate molecules associated with sperm bioenergetic pathways as well as the structural and signaling components of the motility apparatus. The impact of ROS also extends to lesions in the paternal genome, as is commonly seen in the defective spermatozoa of asthenozoospermic males. Concluding, the presence of OS in the male reproductive tract is strongly and positively correlated with reduced sperm motility and fertilizing potential, thus providing a rational target for the development of new therapeutic interventions.

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Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents

Virology Journal ◽

10.1186/s12985-020-01415-w ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Sumanth Khadke ◽

Nayla Ahmed ◽

Nausheen Ahmed ◽

Ryan Ratts ◽

Shine Raju ◽

...

Keyword(s):

Immune System ◽

Viral Replication ◽

Tissue Injury ◽

Phase 1 ◽

Therapeutic Interventions ◽

World Health ◽

Published Data ◽

Cytokine Storm ◽

Host Interactions ◽

Immunological Mechanisms

Abstract Background Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. Discussion We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. Conclusion Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.

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