MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and invasive type of pancreatic cancer (PCa) and is expected to be the second most common cause of cancer-associated deaths. The high mortality rate is due to the asymptomatic progression of the clinical features until the advanced stages of the disease and the limited effectiveness of the current therapeutics. Aberrant expression of several microRNAs (miRs/miRNAs) has been related to PDAC progression and thus they could be potential early diagnostic, prognostic, and/or therapeutic predictors for PDAC. miRs are small (18 to 24 nucleotides long) non-coding RNAs, which regulate the expression of key genes by targeting their 3′-untranslated mRNA region. Increased evidence has also suggested that the chemoresistance of PDAC cells is associated with metabolic alterations. Metabolic stress and the dysfunctionality of systems to compensate for the altered metabolic status of PDAC cells is the foundation for cellular damage. Current data have implicated multiple systems as hallmarks of PDAC development, such as glutamine redox imbalance, oxidative stress, and mitochondrial dysfunction. Hence, both the aberrant expression of miRs and dysregulation in metabolism can have unfavorable effects in several biological processes, such as apoptosis, cell proliferation, growth, survival, stress response, angiogenesis, chemoresistance, invasion, and migration. Therefore, due to these dismal statistics, it is crucial to develop beneficial therapeutic strategies based on an improved understanding of the biology of both miRs and metabolic mediators. This review focuses on miR-mediated pathways and therapeutic resistance mechanisms in PDAC and evaluates the impact of metabolic alterations in the progression of PDAC

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPARγ and C/EBPα); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.publishedVersio

DecodExpo

This set contains data obtained during human bio monitoring study conducted during DecodExpo Project.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

DecodExpo

This set contains data obtained during human bio monitoring study conducted during DecodExpo Project.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

DecodExpo

This set contains data obtained during human bio monitoring study conducted during DecodExpo Project.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach

This in silico toxicogenomic study aims to explore the relationship between phthalates and bisphenol A (BPA) co-exposure and obesity, as well as its comorbid conditions, in order to construct a possible set of genomic biomarkers. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org ) was used as the main data mining tool, along with GeneMania (https://genemania.org), ToppGene Suite (https://toppgene.cchmc.org ) and DisGeNET (http://www. disgenet.org). Among the phthalates, bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) were chosen as the most frequently curated phthalates in CTD, which also share similar mechanisms of toxicity. DEHP, DBP and BPA interacted with 84, 90 and 194 obesity-related genes/proteins, involved in 67, 65 and 116 pathways, respectively. Among these, 53 genes/proteins and 42 pathways were common to all three substances. 31 genes/proteins had matching interactions for all three investigated substances, while more than half of these genes/proteins (56.49%) were in co-expression. 7 of the common genes/proteins (6 relevant to humans: CCL2, IL6, LPL, PPARG, SERPINE1, and TNF) were identified in all the investigated obesity comorbidities, while PPARG and LPL were most closely linked to obesity. These genes/proteins could serve as a target for further in vitro and in vivo studies of molecular mechanisms of DEHP, DBP and BPA mixture obesogenic properties. Analysis reported here should be applicable to any mixture of environmental chemicals and any disease present in CTD