Articles That Use the Tag Name:

reactive oxygen species

Current siRNA Targets in Atherosclerosis and Aortic Aneurysm

Abstract: Atherosclerosis (ATH) and aortic aneurysms (AA) remain challenging chronic diseases that confer high morbidity and mortality despite advances in medical, interventional, and surgical care. RNA interference represents a promising technology that may be utilized to silence genes contributing to ATH and AA. Despite positive results in preclinical and some clinical feasibility studies, challenges such as target/sequence validation, tissue specificity, transfection efficiency, and mitigation of unwanted off-target effects remain to be addressed. In this review the most current targets and some novel approaches in siRNA delivery are being discussed. Due to the plethora of investigated targets, only studies published between 2010 and 2014 were included. ... Read more

Advances in Mechanisms of Anti-oxidation

Abstract: Reactive oxygen species (ROS) are a family of molecules that are continuously produced from oxygen consumption in aerobic cells. Controlled generation of ROS in normal cells serves useful purposes to regulate important cellular processes such as cell proliferation, inflammation, and immune response, but overproduction of ROS causes oxidative stress that contributes to the development of cancer, chronic disease, and aging. These hugely different consequences of ROS exposure demand a carefully balanced control of ROS production and disposition, which is largely achieved through the body's elaborate antioxidant system. The human antioxidant system consists of small antioxidants, antioxidant proteins, ROS-metabolizing enzymes, as well as many regulator proteins that mediate adaptive responses to oxidant stress. How such a complex system reacts with oxidants and achieves the required specificity and sensitivity for proper anti-oxidation is incompletely understood. In this respect, new advances in the understanding of the chemistry that determines the reaction of a given oxidant or antioxidant with a protein target provide considerable insights into these and related questions. The findings hold certain promise for new drug development for preventing and treating diseases associated with oxidant tissue damage. ... Read more

Mitochondria, Prostate Cancer, and Biopsy Sampling Error

Abstract: Mitochondria and their associated genome are emerging as sophisticated indicators of prostate cancer (PCa) biology. Alterations in the mitochondrial genome (mtgenome) have been implicated in cell proliferation, metastatic behavior, androgen independence, as a signal for apoptosis, and as a predictor of biochemical recurrence. Somatic mutation patterns in complete mtgenomes are associated with prostate specific antigen levels (PSA) in PCa patients and a large-scale mtgenome deletion (3.4kb) is consistent with a prostate "cancerization" field effect. This review will focus on the biological characteristics of mitochondria and their direct clinical application to PCa. Mitochondrial science is currently influencing clinical PCa diagnostics and the rapid progress in this area indicates future, break-through contributions in the general field of oncology. ... Read more

Sympathetic Overactivity and Cardiovascular Disease in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Abstract: Cardiovascular disease plays an important role regarding the morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Sympathetic overactivity has been suggested to underpin the association between COPD and the development of cardiovascular disease. However, the pathophysiological basis by which sustained sympathetic overactivity affects cardiovascular function in patients with COPD is complex and incompletely understood. Different simple and more sophisticated measures of sympathetic activity, such as assessment of heart rate, blood pressure variability, and baroreflex sensitivity, provide information on the potential dysregulation of the autonomous nervous system. This review summarizes the findings from studies in animal models and humans on the potential relationship between COPD, sympathetic overactivity, and cardiovascular disease. There is preliminary evidence of sympathetic overactivity in COPD. However, direct evidence of a cause-effect relationship between sympathetic overactivity and cardiovascular disease from studies in COPD patients is lacking. Data from large cohorts of COPD patients and well-designed interventional studies looking at the relationship between COPD and autonomic nervous system function are urgently needed, hopefully leading to novel therapeutic and preventive approaches in the care of patients with COPD. ... Read more

Inflammation in Aging: Cause, Effect, or Both?

Abstract: Aging is a progressive degenerative process tightly integrated with inflammation. Cause and effect are not clear. A number of theories have been developed that attempt to define the role of chronic inflammation in aging: redox stress, mitochondrial damage, immunosenescence, endocrinosenescence, epigenetic modifications, and age-related diseases. However, no single theory explains all aspects of aging; instead, it is likely that multiple processes contribute and that all are intertwined with inflammatory responses. Human immunodeficiency virus (HIV)-infected patients undergo a premature aging phenomenon which may provide clues to better elucidate the nature of inflammation in aging. Environmental and lifestyle effectors of inflammation may also contribute to modulation of both inflammation and age-related dysfunction. ... Read more

Is Obstructive Sleep Apnea a Risk Factor for Diabetes?

Abstract: Obstructive sleep apnea (OSA) and type 2 diabetes are both closely related to obesity and their prevalence is increasing due to the rising average body weight in Western countries. The findings of epidemiological studies have implicated that OSA increases the risk for cardiovascular disease, and metabolic disturbances, such as insulin resistance, may link OSA to vascular morbidity. A number of observational clinical studies have evaluated the relationship between OSA and insulin resistance, suggesting an independent association. However, the confounding effect of obesity complicates the establishment of a causal relationship between OSA and insulin resistance. Potential mechanisms that may underpin this relationship were evaluated in animal and human experimental studies and include intermittent hypoxia, arousals from sleep with concomitant sympathetic activation and sleep fragmentation. Currently only three randomized controlled trials investigating the effects of OSA on insulin resistance have been published. In these trials OSA patients were randomly assigned to treatment with continuous positive airway pressure (CPAP) or subtherapeutic CPAP and treatment effects on various measures of insulin resistance were examined. In two of these trials there was no effect of CPAP on glucose metabolism and in one trial a small beneficial effect of CPAP was observed. Further carefully conducted clinical studies and randomized controlled interventional CPAP trials are needed to determine the extent to which OSA is a risk factor for diabetes and its effect on glucose metabolism. ... Read more

Therapeutic Photobiomodulation: Nitric Oxide and a Novel Function of Mitochondrial Cytochrome C Oxidase

Abstract: Currently, light therapies are widely used in both human and veterinarian medicine. The application of light to clinical therapeutics includes: photodynamic therapy, used to kill cancer cells; UVA therapies, used to treat a variety of skin diseases; and photobiomodulation, used to promote cell growth and recovery from injury. Photobiomodulation uses light emitting diodes (LEDs) or low energy lasers, which emit light in the visible red to near infrared range. Light in this range penetrates tissue reasonably well, lacks the carcinogenic/mutagenic properties of UV light, and acts on an endogenous photoreceptor which likely acts to initiate light-altered signaling pathways. Although early studies identified mitochondrial cytochrome c oxidase as an endogenous photoreceptor for photobiomodulation, the cellular and molecular mechanisms underlying photobiomodulation have not been clear. Three recent findings provide important new insight. First, nitric oxide has been implicated. Second, cytochrome c oxidase, an enzyme known to reduce oxygen to water at the end of the mitochondrial respiratory chain, has been shown to have a new enzymatic activity -- the reduction of nitrite to nitric oxide. This nitrite reductase activity is elevated under hypoxic conditions but also occurs under normoxia. And third, low intensity light enhances nitric oxide synthesis by cytochrome c oxidase without altering its ability to reduce oxygen. From these findings, we propose that cytochrome c oxidase functions in photobiomodulation by producing nitric oxide, a signaling molecule which can then function in both intra- and extracellular signaling pathways. We also propose that the effectiveness of photobiomodulation is under the control of tissue oxygen and nitrite levels. ... Read more

Mitochondria-targeted Antioxidants as Therapies

Abstract: Mitochondria are central to oxidative phosphorylation and much of metabolism, and are also involved in many aspects of cell death. Consequently, mitochondrial dysfunction contributes to a wide range of human pathologies. In many of these, excessive oxidative damage is a major factor because the mitochondrial respiratory chain is a significant source of the damaging reactive oxygen species superoxide and hydrogen peroxide. However, despite the clinical importance of mitochondrial oxidative damage, antioxidants have been of limited therapeutic success. This may be because the antioxidants are not selectively taken up by mitochondria, but instead are dispersed throughout the body. To address this unmet need, a series of mitochondria-targeted antioxidants have been developed over the past few years that are selectively concentrated within mitochondria in vivo. The accumulation of an antioxidant at the site where it is needed most has been shown to improve the outcome in a large number of animal models of diseases that involve mitochondrial oxidative damage. Mitochondria-targeted antioxidants have also been developed as pharmaceuticals and have been shown to be safe and effective in human clinical trial phase IIa studies. Therefore the mitochondria-targeted antioxidants are a new class of pharmaceuticals that can be used in a wide range of human pathologies for which current therapies are of limited efficacy. Here we survey the work that has been done to date using mitochondria-targeted antioxidants and suggest future applications. ... Read more

Endotherapia: A New Frontier in the Treatment of Multiple Sclerosis and Other Chronic Diseases

Abstract: Currently, several drugs are accessible for the treatment of many chronic diseases (multiple sclerosis, amyotrophic lateral sclerosis, rheumatoid arthritis, etc.), but most of them have a large list of side effects. Here, we propose a new therapeutic approach called Endotherapia for the treatment of chronic diseases. This approach combines a biomedical evaluation of circulating immunoglobulins directed against specific self-antigens and self-antigens modified by free radicals. The therapy proposed here is a "tailor-made" combination of small molecules (e.g., fatty acids and vitamins) linked to a non-immunogenic chain of poly-L.Lysine (PLL). Each individual linkage or PLL derivative offers great advantages, such as an increase in the half-life of the active small molecules. Endotherapia also involves clinical aspects, allowing an exact diagnosis of the disease and the identification of specific circulating antibodies in the serum of patients in several clinical trials (e.g., multiple sclerosis). Endotherapia has been shown to be very safe. In summary, Endotherapia is the result of an immunopathological strategy addressing chronic incurable diseases with a multifactorial etiology. In light of the results obtained, it seems that Endotherapia is a promising therapy for chronic diseases, with no side effects, which is evidently mandatory in the management of long-term pathologies. ... Read more

Antioxidant Drugs for Treating Beta-cell Oxidative Stress in Type 2 Diabetes: Glucose-centric Versus Insulin-centric Therapy

Abstract: Mainstays of therapy for type 2 diabetes involve drugs that are insulin-centric, i.e., they are designed to increase insulin secretion and decrease insulin resistance. The usual clinical course for people so treated is to have initially improved glycemic control but over time a need for intensification of drug-based treatment of hyperglycemia. The mechanism for this unrelenting deterioration of β-cell function is related to chronic oxidative stress. This suggests that drug discovery should not exclusively focus on insulin-centric targets, but also include glucose-centric strategies, such as antioxidant protection of the β-cell. This may facilitate repair of β-cells undergoing damage by oxidative stress secondary to chronic hyperglycemia. ... Read more

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