Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes (T2D) and HCV infection are common conditions involving, respectively, at least 170 and 130 million people worldwide. However, the distribution of such cases does not overlap in the same age groups in different geographic areas. Following pioneering reports of increased prevalence of T2D in HCV-positive cirrhosis, interest concerning the relationship between HCV and T2D has escalated. HCV is able to induce insulin resistance (IR) directly and the role of specific viral genotypes responsible for such effect is disputed. IR has consistently been found to be closely linked to fibrosis in HCV infection, although also typically associated with T2D in prefibrotic stages. HCV infection could be associated with a reduced prevalence of metabolic syndrome owing to virus-associated reduction in BMI (reported in population but not clinical studies) and hypobetaliproteinemia. A three- to ten-fold increased risk of HCV infection was reported among diabetic patients in comparison with different control groups and a meta-analysis showed a 1.8-fold excess risk of T2D among HCV-positive compared with HBV-positive patients. Moreover, HCV positivity is associated with an increased risk of T2D in patients receiving liver or kidney transplantations. T2D and IR are independent predictors of a more rapid progression of liver fibrosis and impaired response to antiviral treatment in chronic hepatitis C. Patients with cirrhosis and T2D have an increased susceptibility to hepatic encephalopathy and hepatocellular carcinoma (HCC). However, the beneficial effects of antiviral treatment on IR and T2D are controversial. Theoretically, glycemic control in chronic hepatitis C, and particularly in cirrhotic patients, could improve the prognosis and the response to antivirals, although the evidence for this is limited. Future studies should elucidate the relationship between insulin signaling, HCV and interferon signaling, entity of cardiovascular risk in patients with HCV infection, the potential role of 'metabolic' strategies added to antiviral treatment schedules, the impact of IR on liver failure, portal hypertension and HCC, particularly in patients managed in a transplant setting.
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PMID:Hepatitis C and diabetes: the inevitable coincidence? 1934 43

Helicobacter pylori (H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common infectious pathogen of the gastroduodenal tract. Although its chronic infection is associated with gastritis, peptic ulcer, dysplasia, neoplasia, MALT lymphoma and gastric adenocarcinoma, it has been suggested the possible association of H. pylori infection with several extragastric effects including hepatobiliary and pancreatic diseases. Since a microorganism resembling H. pylori was detected in samples from patients with hepatobiliary disorders, several reports have been discussed the possible role of bacteria in hepatic diseases as hepatocellular carcinoma, cirrhosis and hepatic encephalopathy, nonalcoholic fatty liver disease and fibrosis. Additionally, studies have reported the possible association between H. pylori infection and pancreatic diseases, especially because it has been suggested that this infection could change the pancreatic physiology. Some of them have related a possible association between the microorganism and pancreatic cancer. H. pylori infection has also been suggested to play a role in the acute and chronic pancreatitis pathogenesis, autoimmune pancreatitis, diabetes mellitus and metabolic syndrome. Considering that association of H. pylori to liver and pancreas diseases needs further clarification, our work offers a review about the results of some investigations related to the potential pathogenicity of H. pylori in these extragastric diseases.
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PMID:Extragastric manifestations of Helicobacter pylori infection: Possible role of bacterium in liver and pancreas diseases. 2673 Feb 76

The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.
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PMID:Fecal microbiota transplantation beyond Clostridioides difficile infections. 3120 Nov 41

Autotaxin (ATX) is a soluble extracellular enzyme that is abundant in mammalian plasma and cerebrospinal fluid (CSF). It has two known enzymatic activities, acting as both a phosphodiesterase and a phospholipase. The majority of its biological effects have been associated with its ability to liberate lysophosphatidic acid (LPA) from its substrate, lysophosphatidylcholine (LPC). LPA has diverse pleiotropic effects in the central nervous system (CNS) and other tissues via the activation of a family of six cognate G protein-coupled receptors. These LPA receptors (LPARs) are expressed in some combination in all known cell types in the CNS where they mediate such fundamental cellular processes as proliferation, differentiation, migration, chronic inflammation, and cytoskeletal organization. As a result, dysregulation of LPA content may contribute to many CNS and PNS disorders such as chronic inflammatory or neuropathic pain, glioblastoma multiforme (GBM), hemorrhagic hydrocephalus, schizophrenia, multiple sclerosis, Alzheimer's disease, metabolic syndrome-induced brain damage, traumatic brain injury, hepatic encephalopathy-induced cerebral edema, macular edema, major depressive disorder, stress-induced psychiatric disorder, alcohol-induced brain damage, HIV-induced brain injury, pruritus, and peripheral nerve injury. ATX activity is now known to be the primary biological source of this bioactive signaling lipid, and as such, represents a potentially high-value drug target. There is currently one ATX inhibitor entering phase III clinical trials, with several additional preclinical compounds under investigation. This review discusses the physiological and pathological significance of the ATX-LPA-LPA receptor signaling axis and summarizes the evidence for targeting this pathway for the treatment of CNS diseases.
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PMID:Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases. 3136 25

The progression of liver disease is portrayed by several common, overarching signs and symptoms. Classically, these include findings such as spider angiomata, jaundice, palmar erythema, and as cirrhosis decompensates, ascites, variceal hemorrhage (VH), hepatic encephalopathy (HE), and hepatocellular carcinoma (HCC). Aside from these universal hallmarks among cirrhotics, patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) harbor their own distinct systemic associations and manifestations. NAFLD is tightly linked to metabolic syndrome, which appears to be a driving force for a multitude of comorbidities, such as insulin resistance, cardiovascular disease, chronic kidney disease (CKD), obstructive sleep apnea (OSA), as well as increased malignancy risk. ALD also maintains a variety of comorbidities congruent with systemic effects of chronic alcohol use. These findings are highlighted by cardiovascular conditions, neuronal damage, myopathy, nutritional deficiencies, chronic pancreatitis, in addition to increased malignancy risk. While a general, guideline-driven management for all cirrhotic patients remains imperative for minimizing risk of complications, a tailored treatment strategy is useful for patients with NAFLD and ALD who entertain their own constellation of unique systemic manifestations.
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PMID:Nonalcoholic fatty liver disease and alcoholic liver disease: metabolic diseases with systemic manifestations. 3162 Jun 47