Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Perlina A[original query] |
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A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.
Ruiz P , Perlina A , Mumtaz M , Fowler BA . Environ Health Perspect 2015 124 (7) 1034-41 BACKGROUND: A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. OBJECTIVES: To assess the underlying mechanisms of POPs that have been associated with metabolic diseases, 3 well-known POPs (2,3,7,8-Tetrachlorodibenzodioxin (TCDD), 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153), and p,p'-Dichlorodiphenyldichloroethylene (p,p'-DDE)) were studied. We used advanced database search tools to delineate testable hypotheses and guide laboratory-based research studies into underlying mechanisms by which this POPs mixture could produce or exacerbate metabolic diseases. METHODS: For these studies searches, a proprietary systems biology software MetaCoreTM/MetaDrugTM was used to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within 2 or less interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimental well-documented causal associations with type 2 diabetes. CONCLUSIONS: Our systems biology approach allowed identification of converging pathways leading to activation of common targets downstream. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of 3 common POPs, using a systems biology approach, which may link POPs exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of POPs' effects, which could translate into disease prevention and more effective clinical treatment strategies. |
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