Gene/Protein Disease Symptom Drug Enzyme Compound
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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoriasis is a chronic, inflammatory, immune-mediated skin disease associated with substantial comorbidity. Traditional comorbid conditions include psychological/psychiatric disorders, psoriatic arthritis and inflammatory bowel disease. Increasingly, an association with metabolic dysfunction, including obesity and the metabolic syndrome, and cardiovascular disease, with consequent effects on morbidity and mortality, has been recognized in psoriasis. The underlying inflammatory mechanisms of both psoriasis and psoriasis-associated comorbidities involve mediation by proinflammatory T-helper type 1 cytokines. For effective management of psoriasis and related comorbidities, an integrated approach targeting both cutaneous and systemic inflammation may be beneficial, and strategies to improve overall management of the patient should be encouraged to reduce the disease burden. This paper discusses the emerging role of biological agents in this approach, and offers an appreciation of the role of existing anti-psoriasis and adjunctive therapies.
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PMID:Long-term prognosis in patients with psoriasis. 1870 Sep 9

The melanocortins (alpha, beta and gamma-melanocyte-stimulating hormones: MSHs; adrenocorticotrophic hormone: ACTH), a family of pro-opiomelanocortin (POMC)-derived peptides having in common the tetrapeptide sequence His-Phe-Arg-Trp, have progressively revealed an incredibly wide range of extra-hormonal effects, so to become one of the most promising source of innovative drugs for many, important and widespread pathological conditions. The discovery of their effects on some brain functions, independently made by William Ferrari and David De Wied about half a century ago, led to the formulation of the term "neuropeptide" at a time when no demonstration of the actual production of peptide molecules by neurons, in the brain, was still available, and there were no receptors characterized for these molecules. In the course of the subsequent decades it came out that melanocortins, besides inducing one of the most complex and bizarre behavioural syndromes (excessive grooming, crises of stretchings and yawnings, repeated episodes of spontaneous penile erection and ejaculation, increased sexual receptivity), play a key role in functions of fundamental physiological importance as well as impressive therapeutic effects in different pathological conditions. If serendipity had been an important determinant in the discovery of the above-mentioned first-noticed extra-hormonal effects of melanocortins, many of the subsequent discoveries in the pharmacology of these peptides (feeding inhibition, shock reversal, role in opiate tolerance/withdrawal, etc.) have been the result of a planned research, aimed at testing the "pro-nociceptive/anti-nociceptive homeostatic system" hypothesis. The discovery of melanocortin receptors, and the ensuing synthesis of selective ligands with agonist or antagonist activity, is generating completely innovative drugs for the treatment of a potentially very long list of important and widespread pathological conditions: sexual impotence, frigidity, overweight/obesity, anorexia, cachexia, haemorrhagic shock, other forms of shock, myocardial infarction, ischemia/reperfusion-induced brain damage, neuropathic pain, rheumathoid arthritis, inflammatory bowel disease, nerve injury, toxic neuropathies, diabetic neuropathy, etc. This review recalls the history of these researches and outlines the pharmacology of the extra-hormonal effects of melanocortins which are produced by an action at the brain level (or mainly at the brain level). In our opinion the picture is still incomplete, in spite of being already so incredibly vast and complex. So, for example, several of their effects and preliminary animal data suggest that melanocortins might be of concrete effectiveness in one of the areas of most increasing concern, i.e., that of neurodegenerative diseases.
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PMID:Brain effects of melanocortins. 1899 99

The mammalian GI tract contains a large and diverse ecosystem of microorganisms that play a profound role in our development and physiology. Interestingly, the microbial make-up within the intestine has been found to be altered in many clinically important diseases, including inflammatory bowel disease, irritable bowel syndrome, Types 1 and 2 diabetes, and obesity. Barman et al. used a Salmonella-induced murine model of gastroenteritis to show that the intestinal microbiota are transiently altered during the host inflammatory response to infection. These findings are of interest as understanding how the microbiota are altered during disease states may offer insight into which microbial populations are important in maintaining intestinal homeostasis. Recently, probiotics have been shown to modulate the mucosal immune system and improve intestinal barrier function, validating their potential as therapeutics for gastrointestinal-associated diseases. As we begin to understand the benefits conferred to the intestine by microbiota, the use of probiotics to modify its composition is an attractive option to improve human health.
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PMID:Intestinal microbiota are transiently altered during Salmonella-induced gastroenteritis. 1816 Apr 81

The ability of fat tissue cells to produce proinflammatory cytokines and the concept that obesity represents a low-grade inflammatory response have been well documented during the past decade. The effects of fat-mediated inflammation on metabolic pathologies have also been drawing increasing interest. However, very little is known on the potential effects of adipose tissue in the pathophysiology of gastrointestinal diseases with an inflammatory component, such as inflammatory bowel disease (IBD). The development of large fat masses around the inflamed intestine during Crohn's disease makes this tissue a candidate for more intense investigation in studies aiming to gain insights into the pathogenesis and progress of the disease. Furthermore, neuropeptides act in many cases in a proinflammatory manner and are shown to participate in the pathogenesis of intestinal inflammation in animal models of IBD. However, the potential of these molecules to interact with fat cells in the context of IBD has not been investigated. In this review the authors' most recent data related to the effects of neuropeptides on noninflammatory fat tissue components are described. In addition, a discussion to associate neuropeptide-induced, adipose tissue-mediated responses with the generation of intestinal inflammatory conditions such as Crohn's disease is included.
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PMID:Neuropeptides, mesenteric fat, and intestinal inflammation. 1907 72

To analyze the vast number and variety of microorganisms inhabiting the human intestine, emerging metagenomic technologies are extremely powerful. The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, helping to maintain their homeostasis and can be causative of various diseases, such as inflammatory bowel disease and obesity. A simplified animal model system has provided the mechanistic basis for the molecular interactions that occur at the interface between such microbes and host intestinal epithelia. Through metagenomic analysis, it is now possible to comprehensively explore the genetic nature of the intestinal microbiome, the mutually interacting system comprising the host cells and the residing microbial community. The human microbiome project was recently launched as an international collaborative research effort to further promote this newly developing field and to pave the way to a new frontier of human biology, which will provide new strategies for the maintenance of human health.
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PMID:The human intestinal microbiome: a new frontier of human biology. 1914 30

Leptin, a protein containing 167 amino acids, demonstrates structural similarities with cytokine family and is mainly produced by adipocytes. The leptin receptor (OB-R) is a large membrane spanning protein that belongs to the gp 130 family of cytokine class I receptors. Besides the neuroendocrine effects of leptin in the control of food intake and energy expenditure, binding of this hormone has been proven in intestine, liver, kidney, skin, stomach, heart, spleen, lung, and so on. Thus leptin affects maternal, fetal and placental function, it appears to act as an endocrine and paracrine factor for the regulation of reproduction and puberty, prevents ectopic lipid deposition, modifies insulin sensitivity in the muscle or liver, and links the immune and endocrine systems. The LEP gene encodes for leptin. It has been localized in humans on the 7 alpha 31.3 chromosome and consists of three exons separated by two introns. In humans, a mutation in the LEP gene was reported in two children with the same cosanguineous pedigree. Other studies reported a polymorphism in the promoter untranslated exon 1 of the LEP gene (A19G), a polymorphism C(-188)A in the promoter region of the LEP gene (17) and a mutation at codon V110M. The biologic activities of leptin on target tissues are carried out through binding to a specific receptor, LEPR. LEPR maps in humans to the 1p31 chromosome. Variants commonly occur, which cause two nonconservative changes:lysine to asparagine at codon 656 (AAG to AAC) in exon 14 (K656N); lysine to arginine at codon 109 (AAG to AGG) in exon 4 (K109R); a nonconservative change glutamine to arginine at codon 223 (CAG to CGG); a silent TC change at codon 343; and a silent GA transition at codon 1019. Leptin is related with obesity and its metabolic disorders. However, new relation ships have been described; inflammatory bowel disease, cancer, bone formation, asthma and so on. In conclusion, despite the great advances in our knowledge of leptin physiology, many areas of investigation remain. Future research is expected to discover new molecules in the leptin pathway, to treat obesity and its related diseases.
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PMID:Leptin and obesity. 1918 39

Acylethanolamides (AEs) are a group of lipids occurring in both plants and animals. The best-studied AEs are the endocannabinoid anandamide (AEA), the anti-inflammatory compound palmitoylethanolamide (PEA), and the potent anorexigenic molecule oleoylethanolamide (OEA). AEs are biosynthesized in the gastrointestinal tract, and their levels may change in response to noxious stimuli, food deprivation or diet-induced obesity. The biological actions of AEs within the gut are not limited to the modulation of food intake and energy balance. For example, AEs exert potential beneficial effects in the regulation of intestinal motility, secretion, inflammation and cellular proliferation. Molecular targets of AEs, which have been identified in the gastrointestinal tract, include cannabinoid CB(1) and CB(2) receptors (activated by AEA), transient receptor potential vanilloid type 1 (TRPV1, activated by AEA and OEA), the nuclear receptor peroxisome proliferators-activated receptor-alpha (PPAR-alpha, activated by OEA and, to a less extent, by PEA), and the orphan G-coupled receptors GPR119 (activated by OEA) and GPR55 (activated by PEA and, with lower potency, by AEA and OEA). Modulation of AE levels in the gut may provide new pharmacological strategies not only for the treatment of feeding disorders but also for the prevention or cure of widespread intestinal diseases such as inflammatory bowel disease and colon cancer.
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PMID:Role of acylethanolamides in the gastrointestinal tract with special reference to food intake and energy balance. 1928 59

The inflammatory bowel diseases (IBDs) are a group of heterogeneous disorders characterized by acute and chronic inflammatory changes in the small or large bowel, or in both. Increasing incidence and prevalence figures for IBD both in the developed and developing world indicate that environmental factors are at least as significant in IBD as genetic susceptibility. Of these, diet and the host microbiota are likely to play important but as yet poorly defined roles. The major constituents of a standard "Western" diet may contribute to, or protect against, intestinal inflammation via several mechanisms. These include the effects of insulin resistance and short-chain fatty acids such as butyrate, modification of intestinal permeability, the antiinflammatory role of polyunsaturated fatty acids, and the effect of sulfur compounds from protein on host microbiota. This detailed review critically assesses the evidence for the role of diet in the development of IBD and examines the evidence for obesity as a contributing factor to IBD pathogenesis. Particular attention is focused on methodological issues including suitability of cases and controls, confounders such as smoking, and total energy expenditure.
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PMID:Role of diet in the development of inflammatory bowel disease. 2072 59

The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, leading to maintain their homeostasis, and can be causative of various diseases such as inflammatory bowel disease and obesity. A culture-independent approach 'metagenomics' now makes it possible to comprehensively explore the genetic nature of intestinal microbiome (collective genomes of microbes), providing the mechanistic basis for the functional roles of intestinal microbiome. The International Human Microbiome Project was recently launched to further promote this newly developing field, which will provide new strategies for the maintenance of human health.
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PMID:[Disease and metagenomics of intestinal microbiomes]. 1950 17

The term psoriatic disease encompasses the array of disorders (arthritis, inflammatory bowel disease, uveitis, obesity, metabolic syndrome, type II diabetes, and cardiovascular disease) that are associated with psoriasis. Psoriatic arthritis (PsA) is present in about 25% of patients with psoriasis; in most cases, the psoriasis precedes joint disease by about 10 years. Previous studies revealed that osteoclast precursors (OCP) are elevated in PsA and that the frequency of these circulating cells correlates with bone destruction. More recently OCP were found to be increased also in early rheumatoid arthritis and in 25% of psoriasis patients without arthritis. Bone marrow edema, observed on magnetic resonance imaging, in PsA represents infiltration of underlying marrow with inflammatory cells based on studies in transgenic tumor necrosis factor (TNF) arthritis murine models. Studies in the TNF transgenic mouse model also revealed that changes in lymph node volume precede joint flare. These translational studies point to potential biomarkers of arthritis in psoriasis patients and generate alternative hypotheses to explain the events that lead to arthritic flare.
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PMID:Translational perspectives on psoriatic arthritis. 1966 36


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