Objective To investigate the effect of di-2-ethylhexyl phthalate (DEHP) on the proliferation of SK-N-SH human neuroblastoma cells and its underlying mechanism. Methods Cells were cultured in estrogen-free improved Dulbecco's Modified Eagle's Medium and then divided into 5 groups: no treatment (control group); treated with 17β-estradiol (E_2 group); treated with DEHP (DEHP group); treated with both E_2 and phosphatidylinositol-3-kinases (PI3K) inhibitor LY294002 (E_2 + LY294002 group); treated with both DEHP and LY294002 (DEHP + LY294002 group). The absorbance value (AV) was measured on day 0, 2, and 5. DNA proliferation index (PI) and apoptotic index (AI) were determined by flow cytometry on day 5. Caspase-3 protein, protein-serine-threonine kinase (Akt) and phosphor-Akt (Ser473) protein expression were analyzed by Western blot on day 5. Results The AV of All groups increased on day 2, and 5. The AV of E_2 and DEHP groups were higher than that of the control group (P<0. 001), but the AV of E_2 + LY294002 and DEHP + LY294002 groups were lower than those of E_2 and DEHP groups (P<0.01) on day 2 and 5. On day 5, PI of E_2 and DEHP groups were also higher than that of control (P<0.01). However, PI of E_2 + LY294002 and DEHP + LY294002 groups were lower than those of E_2 and DEHP group (P<0.01) on day 5. There was no significant difference in AI and caspase-3 protein expression among the groups. At the same time, phosphor-Akt (Ser473) protein expression of E_2 and DEHP groups increased obviously, compared with the control group. Compared with E_2 and DEHP groups, E_2 + LY294002 and DEHP + LY294002 groups decreased significantly. However, Akt protein expression was equal among those groups. Conclusions DEHP can promote the growth of SK-N-SH cells to a level similar to that of E_2, with activation of the PI3K/Akt signaling pathway.

AIM:To investigate the effect of liraglutide ( LG) on the expression of fibronectin type Ⅲdomain-containing protein 5 (FNDC5) in the C2C12 myotubes.METHODS:The C2C12 mouse myoblast cell line was induced to differentiation.Differentiated cells were stimulated with gradient concentrations (1 ~1000 nmol/L) of LG for different time (0 ~24 h).The effects of LG on the expression of FNDC5 and the activation of adenosine 5'-monophosphate ( AMP)-activated protein kinase ( AMPK) signaling pathway were determined .After pretreated with glucagon-like peptide-1 ( GLP-1 ) receptor antagonist exendin 9-39 , the inhibitor of Ca 2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2), STO609, or the inhibitor of AMPK, Compound C, the LG-induced FNDC5 expression in C2C12 myotubes was examined.The expression of FNDC5 and the activation of AMPK were determined by Western blot .RESULTS: In C2C12 myotubes, LG promoted the expression of FNDC5 in a dose-and time-dependent manner .LG also activated AMPK signaling pathway .These effects of LG were partly abolished by exendin 9-39 , STO609 and Compound C .CONCLUSION:LG promotes the expression of FNDC5 via GLP-1 receptor in the C2C12 myotubes possibly through activation of the CAMKK2/AMPK signaling pathways .

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m³ increase of gestational exposure to PM_2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1^st-2^nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O₃ exposure during the 1^st week and SO₂ exposure during 6^th-7^th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS This study highlighted that gestational exposure to PM_2.5, O₃, and SO₂ had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.
Infant ; Pregnancy ; Child ; Humans ; Female ; Air Pollutants/analysis* ; Case-Control Studies ; Prenatal Exposure Delayed Effects/epidemiology* ; Heart Defects, Congenital/etiology* ; China/epidemiology* ; Particulate Matter/adverse effects* ; Maternal Exposure/adverse effects*

Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and lethal tumor with poor prognosis. Its survival period ranges from four months to one year, and the 5-year survival rate is only about 10%. MPM is highly resistant to chemotherapy, and conventional treatments such as cisplatin combined with pemetrexed or raltitrexed only have a certain effect in about 20% of patients. In recent years, with the continuous in-depth understanding of the genetic variation characteristics of MPM, some progress has been made in the molecular mechanism underlying the chemotherapy resistance of MPM. This article will summarize the research progress of the molecular mechanism underlying the chemotherapy resistance of MPM, including BAP1 gene mutation, microRNA, MTA1-mediated DNA damage repair pathway, GITR-GITRL pathway, TGFa pathway, tumor stem cell, EGFR, and PTEN. The aim of this work is to provide a reference for exploring new therapeutic targets and combined treatment options for MPM.