Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep is an important component of mammalian homeostasis, vital for survival. Sleep disorders are common in the general population and are associated with significant medical, psychologic, and social disturbances. Sleep, in particular deep sleep, has an inhibitory influence on the HPA axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is associated with a 24-hour increase of ACTH and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. Sleepiness and fatigue are very prevalent in the general population, and recent studies have demonstrated that the proinflammatory cytokines IL-6 and/or TNF-alpha are elevated in disorders associated with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia. Sleep deprivation leads to sleepiness and daytime hypersecretion of IL-6. Combined, these findings suggest that the HPA axis stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive daytime sleepiness in humans.
 ...
PMID:Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. 1205 86

Recently, a clinical study provided evidence that treatment of endometriotic women with human chorionic gonadotrophin (hCG) alleviates disease-related pain and sleeplessness suggesting therapeutic effects of the hormone. Since endometriosis is associated with aberrant concentrations of inflammatory mediators in the peritoneal fluid, we investigated whether hCG may affect cytokine-dependent activation of the key-regulatory transcription factor NF-kappaB and expression of two nuclear factor kappa B (NF-kappaB)-inducible genes, tumour necrosing factor (TNF-alpha) and interleukin (IL)-1beta, in stromal cells isolated from ectopic endometriotic tissues. Electrophoretic mobility shift assay revealed that treatment of these cultures with the urinary preparation hCG-A suppressed TNF-alpha- or IL-1beta-induced NF-kappaB DNA-binding activity, whereas another urinary hCG preparation (hCG-B) was less effective. Recombinant alphahCG or epidermal growth factor (EGF), a contaminant of some urinary hCG preparations, did not alter cytokine-dependent NF-kappaB activation. Immunofluorescene of its p65 subunit revealed that pre-incubation with hCG-A strongly decreased TNF-alpha-dependent nuclear expression of NF-kappaB. Accordingly, hCG-A diminished IL-1beta-induced TNF-alpha transcript levels and protein release measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The hormone also attenuated TNF-alpha-dependent mRNA expression of IL-1beta. Western blot analyses revealed that hCG-A impaired TNF-alpha-mediated phosphorylation and degradation of the inhibitor IkappaBalpha suggesting that the hormone may reduce nuclear import of NF-kappaB by stabilizing its inhibitor. The data suggest that hCG attenuates inflammation-dependent NF-kappaB activation and cytokine expression that could provide one explanation for the beneficial role of the hormone in endometriotic patients.
 ...
PMID:Human chorionic gonadotrophin attenuates NF-kappaB activation and cytokine expression of endometriotic stromal cells. 1752 69

Armillariella mellea (AM), also known as Mi-Huan-Ku, a popular medicinal fungus used in the traditional Chinese medicine for treating headache, neurasthenia and insomnia. In the present study, our aim was to determine the effects of aqueous (AAM) and ethanol (EAM) extracts of A. mellea on lipopolysaccharide (LPS)-induced inflammatory response by measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-1 and -2 (COX-1 and COX-2) protein expression, cytokines (TNF-alpha, IL-4 and IL-8) formation, nitric oxide (NO) release and prostaglandin (PGE(2)) production in human monocytic (THP-1) cells. At concentration of 100 microg/ml, EAM, but not AAM, effectively protected against LPS-induced cell death in THP-1 cells. At concentrations of 10 approximately 100 microg/ml, EAM showed a potent anti-inflammatory activity as demonstrated by a dose-dependent inhibition of LPS (1 microg/ml)-induced release of NO and PGE(2), and significantly decreased the transcription of proinflammatory cytokines. EAM at 100 mug/ml significantly blocked the LPS induction of iNOS and COX-2 expression, but not COX-1. Therefore, the protective effect of EAM against LPS-induced inflammatory mediators release could explain, at least in part, its effectiveness in alleviating certain inflammatory related diseases.
 ...
PMID:Armillariella mellea shows anti-inflammatory activity by inhibiting the expression of NO, iNOS, COX-2 and cytokines in THP-1 cells. 1759 9