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Graphical abstract DEHP exposure promotes and aggravates carbon tetrachloride-induced liver fibrogenesis and destroyed the pathophysiological integrity of the liver in rats. DEHP-induced hepatotoxicity is associated with oxidative stress, which could be mediated by SOD and GSH defense response. DEHP exposure activated the TGF-β1/Smad and p38MAPK/NF-κB signaling pathway to induced inflammatory response in the liver. Highlights • The exposed DEHP dose is close to human daily exposure. • DEHP can aggravate the formation of hepatic fibrosis. • DEHP causes oxidative stress and inflammatory reaction to aggravate liver damage. • TGF-β1/Smad and p38MAPK/NF-κB signaling pathways play a key role in hepatic fibrosis induced by DEHP. Abstract Di(2-ethylhexyl) phthalate (DEHP) is an environmental pollutant that is widely used in medical and consumer products. An epidemiological study has suggested that a large daily intake of DEHP from phthalate-contaminated food may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and exacerbates the progression of chronic liver injury. However, the effect of DEHP on hepatic fibrosis is rarely studied. In the present study, we sought to determine the effect of DEHP on carbon tetrachloride (CCl4)-induced liver fibrosis, and to further examine the molecular mechanisms. We found that DEHP exposure remarkably promoted liver inflammation, necrosis and fibrosis, and increased expression of the protein associated with liver inflammation and fibrogenesis, including α-SMA, COL-Ⅰ, COL-Ⅲ, TGF-β1, P-Smad2, P-Smad3, P-p38 and P-p65. The similar trend was observed in the LX-2 cells. Furthermore, DEHP exposure induced oxidative stress and inflammatory cytokine production. Taken together, DEHP might play a fibrotic role in hepatic fibrosis rats and TGF-β1-stimulated LX-2 cells in vitro which was related to TGF-β1/Smad and p38MAPK/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) may be responsible for inducing alterations similar to those encountered in nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate the detrimental effects and possible mechanisms of DEHP on fatty liver rats directly through triggering the disorder of liver lipid metabolism or indirectly by hepatotoxic effect. Considering these effects, DEHP may play a significant role in the pathogenesis of NAFLD. In this study, high-fat diet was used to induce NAFLD in rats for eight weeks. DEHP treated groups received (0.05, 5, 500 mg/kg daily, respectively) dose by gavage during the whole experiment period. Our results indicated that the detrimental effects of DEHP on high-fat diet induced NAFLDs were mediated via increasing lipid accumulation in the liver and causing lipid peroxidation and inflammation. [ABSTRACT FROM AUTHOR]

Background and Aims: Human epidermal growth factor receptor (EGFR) and HER2 (ErbB2) both belong to EGFR family, which are overexpressed in a significant proportion of cases of gastric cancer (GC). Various studies have evaluated the prognostic value of EGFR or HER level in GC. However, the overall test performance remains unclear. We undertook this study to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of EGFR or HER2 as a predictor of survival time in patients with GC. Methods: Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle–Ottawa Tool. Data were collected comparing overall survival (OS) in patients with high and low EGFR or HER2 level. Studies were pooled and summary hazard ratios were calculated. Results: Studies were listed twice if they provided overall survival data for both EGFR and HER2. Eight studies (seven for EGFR and eight for HER2) were included. Two distinct groups were pooled for analysis and revealed that high EGFR, HER2 levels predicted poor overall (HR = 1.66, 95% CI: 1.35–2.02) and (HR = 1.43, 95% CI: 1.09–1.88) survival. No publication bias was found. Conclusions: This meta-analysis result suggested that EGFR or HER2 should have significant predictive ability for estimating overall survival in GC patients and may be useful for defining prognosis of GC patients. [ABSTRACT FROM AUTHOR]