Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO*) reacts with superoxide (O2-*) forming peroxynitrite (PXN) (ONOO-), a strong oxidant which reacts with several biomolecules leading to enormous implications in biological process, holds enormous implications for the understanding of free radicals. The ONOO- formation in vivo has significant implications in free radical biology. It exerts a defensive role in large number of pathophysiological reactions and also acts as signaling molecule in activation of several protooncogenes. It decomposes rapidly to an intermediate and reacts with several biomolecules. Evidence for PXN formation in vivo has been obtained immunohistochemically through detection of a characteristic reaction product with protein tyrosine residues and 3-nitrotyrosine. This "biomarker" of PXN formation has now been identified in various pathologies such as Lou Gehrig's disease, Parkinson's disease, cancer, atherosclerosis as well as in biological aging. 3-nitrotyrosine formation has been documented in various tissues, e.g. even in non-diseased embryonic heart during normal development. Therefore, there is a great opportunity in the postgenomic period to understand the interplay of these molecular interactions with biological events such as apoptosis, gene regulation etc. This review deals with biological significance of peroxynitrite, its precursors, reactions with large range of biomolecules, including aminoacids, proteins, lipids, nucleic acids, antioxidants as well as cytotoxic aspects.
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PMID:Peroxynitrite: a potent oxidizing and nitrating agent. 1678 14

Alzheimer's disease (AD) is a neurodegenerative disease characterized by gradual cognitive decline, impairments in speech and language, and dysfunction in the sensorimotor systems, culminating in complete reliance on nursing care. Oxidative stress, caused by an imbalance in the pro-oxidant/antioxidant mechanisms in the body, has been implicated in AD pathogenesis, as in many other age-associated diseases such as atherosclerosis, Parkinson disease, and amyotrophic lateral sclerosis. Although the hormones estrogen, progesterone, testosterone, and luteinizing hormone are best known for their roles in reproduction, many studies show these hormones have other roles, including neuroprotection. Changes in the levels of these hormones that occur in reproductive senescence are hypothesized to increase risk of AD, as a result of reduced protection against oxidative insults. The Abeta peptide, overproduction of which is thought to be a key pathogenic event in the development of AD, is neurotoxic, most likely due to its ability to promote oxidative stress. The reproductive hormones are known to influence Abeta metabolism, and this review discusses the beneficial and detrimental effects these hormones have on Abeta production and oxidative stress, and their relevance in potential AD therapies.
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PMID:Reproductive hormones modulate oxidative stress in Alzheimer's disease. 1703 49

Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.
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PMID:Altered lipid metabolism in brain injury and disorders. 1875 14

Reactive oxygen species (ROS) are produced at low levels in mammalian cells by various metabolic processes, such as oxidative phosphorylation by the mitochondrial respiratory chain, NAD(P)H oxidases, and arachidonic acid oxidative metabolism. To maintain physiological redox balance, cells have endogenous antioxidant defenses regulated at the transcriptional level by Nrf2/ARE. Oxidative stress results when ROS production exceeds the cell's ability to detoxify ROS. Overproduction of ROS damages cellular components, including lipids, leading to decline in physiological function and cell death. Reaction of ROS with lipids produces oxidized phospholipids, which give rise to 4-hydroxynonenal, 4-oxo-2-nonenal, and acrolein. The brain is susceptible to oxidative damage due to its high lipid content and oxygen consumption. Neurodegenerative diseases (AD, ALS, bipolar disorder, epilepsy, Friedreich's ataxia, HD, MS, NBIA, NPC, PD, peroxisomal disorders, schizophrenia, Wallerian degeneration, Zellweger syndrome) and CNS traumas (stroke, TBI, SCI) are problems of vast clinical importance. Free iron can react with H(2)O(2) via the Fenton reaction, a primary cause of lipid peroxidation, and may be of particular importance for these CNS injuries and disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Atherosclerosis, the major risk factor for ischemic stroke, involves accumulation of oxidized LDL in the arteries, leading to foam cell formation and plaque development. This review will discuss the role of lipid oxidation/peroxidation in various CNS injuries/disorders.
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PMID:Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. 1962 72

The hypothesis proposed in this article is that a haemodynamic mechanism may cause amyotrophic lateral sclerosis (ALS). The hypothesis is synthesized from three separate streams of medical research: (1) multiple sclerosis (MS) research; (2) ALS research; (3) atherosclerosis research. Each research stream was reviewed as prerequisite for proposing the hypothesis. A vascular mechanism for MS was first advanced in the medical literature 130years ago. Seventy years ago researchers knew that the plaques aligned along a central vein, and the wall of that central vein was damaged and leaky. Twenty-five years ago the refluxing blood mechanism was proposed. Zamboni imaged the veins of MS patients in 2007 and saw stenoses, twistings, and membrane blockages in the jugular, azygous, and vertebral veins, and refluxing venous blood upstream of the constrictions. The refluxing blood damages the blood-brain-barrier (BBB) of the veins. Leakage of blood components into the central nervous system then causes the plaques in the brains of MS people. Zamboni dilated the venous constrictions endovascularly, and the MS symptoms and brain plaques diminished dramatically. ALS research has recently revealed that this disease is started by blood-spinal cord-barrier (BSCB) damage. The ALS mutant mouse shows BSCB damage and down regulation of tight junction proteins Occludin and ZO-1 before motor neuron harm. Samplings of ALS patients' spinal cords show downregulation of mRNA for tight junction proteins compared to controls. Atherosclerosis research provides the mechanism for how the refluxing blood breaks the tight junctions between the endothelial cells of the veins. Atherosclerosis research on blood flow effects shows that normal pulsatile laminar blood flow is necessary for maintenance of the tight junctions between endothelial cells. Abnormal flow conditions, such as turbulent, stopped, or reversed flow, cause downregulation of tight junction proteins Occludin and ZO-1. Blood flow (haemodynamic) effects explain the BBB damage in MS and may explain the BSCB damage in ALS. The hypothesis: ALS is caused by constrictions in veins draining the spinal cord and brain, which cause venous reflux, which downregulates tight junction proteins Occludin and ZO-1, which leads to breaks in the tight junctions between endothelial cells in the veins, which leads to leakage of toxic blood components into CNS tissue. The consequences of the hypothesis are discussed. If a venous constriction can be reached endovascularly it can be dilated, and such dilation may constitute cure of ALS.
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PMID:A possible haemodynamic mechanism for amyotrophic lateral sclerosis. 2040 Feb 30

We propose a new text mining technique to identify associations between biological entities, specifically genes-diseases associations, from the biomedical literature. The proposed method is very simple and straightforward; it uses two sets (a positive set and a negative set) of documents and utilises the concepts of expectation (ex), evidence (ev), and Z-scores in combining positive and negative evidences in determining the significant gene-disease associations from Medline documents. Moreover, the method offers an efficient way to handle gene names, aliases, symbols, and abbreviations. We evaluated the method in discovering gene-to-disease associations from literature and the experimental results are impressive. We verified our results and confirmed the effectiveness of the proposed technique by various ways. For example, we ran the technique on some discovered and known genes-diseases relationships. Our method was able to discover associations between genes and various diseases like Amyotrophic lateral sclerosis, Tuberous Sclerosis, Autism, Homocystinuria, Bipolar Disorder, Atherosclerosis and more.
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PMID:A text-mining technique for extracting gene-disease associations from the biomedical literature. 2061 35

A chronic inflammatory disease is a condition characterized by persistent inflammation. A number of human pathologies fall into this category, and a great deal of research has been conducted to learn more about their characteristics and underlying mechanisms. In many cases, a genetic component has been identified, but also external factors like food, smoke, or environmental pollutants can significantly contribute to worsen their symptoms. Accumulated evidence clearly shows that chronic inflammatory diseases are subjected to a redox control. Here, we shall review the identity, source, regulation, and biological activity of redox molecules, to put in a better perspective their key-role in cancer, diabetes, cardiovascular diseases, atherosclerosis, chronic obstructive pulmonary diseases, and inflammatory bowel diseases. In addition, the impact of redox species on autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and celiac disease) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis) will be discussed, along with their potential therapeutic implications as novel drugs to combat chronic inflammatory disorders.
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PMID:Chronic inflammatory disorders and their redox control: from molecular mechanisms to therapeutic opportunities. 2139 2

The understanding of the essential role of selenium (Se) in human health has increased substantially in recent decades. Micronutrient deficiencies are very common in the general population and may be even more common in patients with different pathologies due to genetic or environmental causes and prescription drug use. Selenium is used by people in the prevention and/or treatment of different disorders including cardiovascular disease, osteoarthritis, rheumatoid arthritis, hypothyroidism, stroke, atherosclerosis, cancer susceptibility and treatment, HIV, AIDS, neuronal diseases such as Alzheimer or amyotrophic lateral sclerosis, pancreatitis, depression, and diabetes amongst others. Several mechanisms have been suggested to mediate the biological effects of Se and these include antioxidant defence systems, synthesis and stability of metabolites that act as intermediates implicated in diverse selenoproteins expression pathways oxidative metabolism, immune system modulation, DNA intercalators, kinase regulation, enzymatic cofactor, and gene expression. A number of clinical trials in recent years have provided convincing evidence of the central role of this element, either alone or in combination with other micronutrients or antioxidants, in the prevention and treatment of multiple diseases. Based on these studies this review focuses on the advances made so far in the study of mechanisms and applications of selenium compounds that could be suitable for chronic diseases.
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PMID:Selenium and clinical trials: new therapeutic evidence for multiple diseases. 2186 84

Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action.
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PMID:Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. 2340

Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein.
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PMID:Minocycline: far beyond an antibiotic. 2344 23


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