Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free radicals derived from oxygen, nitrogen and sulphur molecules in the biological system are highly active to react with other molecules due to their unpaired electrons. These radicals are important part of groups of molecules called reactive oxygen/nitrogen species (ROS/RNS), which are produced during cellular metabolism and functional activities and have important roles in cell signalling, apoptosis, gene expression and ion transportation. However, excessive ROS attack bases in nucleic acids, amino acid side chains in proteins and double bonds in unsaturated fatty acids, and cause oxidative stress, which can damage DNA, RNA, proteins and lipids resulting in an increased risk for cardiovascular disease, cancer, autism and other diseases. Intracellular antioxidant enzymes and intake of dietary antioxidants may help to maintain an adequate antioxidant status in the body. In the past decades, new molecular techniques, cell cultures and animal models have been established to study the effects and mechanisms of antioxidants on ROS. The chemical and molecular approaches have been used to study the mechanism and kinetics of antioxidants and to identify new potent antioxidants. Antioxidants can decrease the oxidative damage directly via reacting with free radicals or indirectly by inhibiting the activity or expression of free radical generating enzymes or enhancing the activity or expression of intracellular antioxidant enzymes. The new chemical and cell-free biological system has been applied in dissecting the molecular action of antioxidants. This review focuses on the research approaches that have been used to study oxidative stress and antioxidants in lipid peroxidation, DNA damage, protein modification as well as enzyme activity, with emphasis on the chemical and cell-free biological system.
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PMID:Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. 1975 73

Activation of the Toll-like receptor 4 (TLR4) complex, a receptor of the innate immune system, may underpin the pathophysiology of many human diseases, including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory disorders, schizophrenia, bipolar disorder, autism, clinical depression, chronic fatigue syndrome, alcohol abuse, and toluene inhalation. TLRs are pattern recognition receptors that recognize damage-associated molecular patterns and pathogen-associated molecular patterns, including lipopolysaccharide (LPS) from gram-negative bacteria. Here we focus on the environmental factors, which are known to trigger TLR4, e.g., ozone, atmosphere particulate matter, long-lived reactive oxygen intermediate, pentachlorophenol, ionizing radiation, and toluene. Activation of the TLR4 pathways may cause chronic inflammation and increased production of reactive oxygen and nitrogen species (ROS/RNS) and oxidative and nitrosative stress and therefore TLR-related diseases. This implies that drugs or substances that modify these pathways may prevent or improve the abovementioned diseases. Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen. The authors posit that activation of the TLR radical (ROS/RNS) cycle is a common pathway underpinning many "civilization" disorders and that targeting the TLR radical cycle may be an effective method to treat many inflammatory disorders.
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PMID:Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. 2343 41

Luteolin inhibited growth of several cancer cells in vitro in previous studies, with limited in vivo studies, and no comprehensive understanding of molecular mechanisms at genomics level. This study identified luteolin as an effective agent to inhibit melanoma cell growth in vitro and in vivo. Molecular studies and genomic profiling were used to identify the mechanism of action of luteolin in melanoma cells. As a ROS (reactive oxygen species) scavenger, luteolin unexpectedly induced ROS; but co-treatment with antioxidants NAC or mito-TEMPO did not rescue cell growth inhibition, although the levels of ROS levels were reduced. Next, we profiled luteolin-induced differentially expressed genes (DEGs) in 4 melanoma cell lines using RNA-Seq, and performed pathway analysis using a combination of bioinformatics software including PharmetRx which was especially effective in discovering pharmacological pathways for potential drugs. Our results show that luteolin induces changes in three main aspects: the cell-cell interacting pathway (extracellular matrix, ECM), the oncogenic pathway and the immune response signaling pathway. Based on these results, we further validated that luteolin was especially effective in inhibiting cell proliferation when cells were seeded at low density, concomitantly with down-regulation of fibronectin accumulation. In conclusion, through extensive DEG profiling in a total of 4 melanoma cell lines, we found that luteolin-mediated growth inhibition in melanoma cells was perhaps not through ROS induction, but likely through simultaneously acting on multiple pathways including the ECM (extracellular matrix) pathway, the oncogenic signaling and the immune response pathways. Further investigations on the mechanisms of this promising compound are warranted and likely result in application to cancer patients as its safety pharmacology has been validated in autism patients.
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PMID:Luteolin inhibits melanoma growth in vitro and in vivo via regulating ECM and oncogenic pathways but not ROS. 3241 25