Preliminary Study on the Protective Effects and Molecular Mechanism of Procyanidins against PFOS-Induced Glucose-Stimulated Insulin Secretion Impairment in INS-1 Cells.

This study aimed to investigate the effects of perfluorooctanesulfonic acid (PFOS) exposure on glucose-stimulated insulin secretion (GSIS) of rat insulinoma (INS-1) cells and the potential protective effects of procyanidins (PC). The effects of PFOS and/or PC on GSIS of INS-1 cells were investigated after 48 h of exposure (protein level: insulin; gene level: glucose transporter 2 (Glut2), glucokinase (Gck), and insulin). Subsequently, the effects of exposure on the intracellular reactive oxygen species (ROS) activity were measured. Compared to the control group, PFOS exposure (12.5, 25, and 50 µM) for 48 h had no significant effect on the viability of INS-1 cells. PFOS exposure (50 µM) could reduce the level of insulin secretion and reduce the relative mRNA expression levels of Glut2, Gck, and insulin. It is worth noting that PC could partially reverse the damaging effect caused by PFOS. Significantly, there was an increase in ROS after exposure to PFOS and a decline after PC intervention. PFOS could affect the normal physiological function of GSIS in INS-1 cells. PC, a plant natural product, could effectively alleviate the damage caused by PFOS by inhibiting ROS activity.

Role of non-neuronal cholinergic system in the early stage response of epithelial-mesenchymal transformation related markers in A549 cells induced by coal particles.

Objective: This study was aimed to investigate the role of non-neuronal cholinergic system (NNCS) in the early stage response of epithelial-mesenchymal transformation (EMT) related markers in human lung adenocarcinoma A549 cells induced by coal particles. Methods: A549 cells were exposed to different concentrations of GBW11110K, GBW11126D and exogenous acetylcholinesterase (AChE) (the exposure doses were determined according to the results of CCK-8 experiment, and the doses that had no significant effects on cell viability were selected) for 24 h. After exposure, the indexes of oxidative stress (SOD and MDA), inflammatory factors (IL-6 and TNF-α), EMT marker proteins (E-cadherin and vimentin), AChE enzymatic activity and mRNA expression levels of different types of acetylcholine receptors (CHRM3, CHRM5, CHRNA5, CHRNA7, CHRNA9 and CHRNB2) were determined. Results: GBW11110K and GBW11126D exposure could lead to the following injury effects: the levels of oxidative stress and inflammatory factors changed to a certain extent (SOD decreased gradually, while MDA, IL-6 and TNF-α increased). The protein level of E-cadherin decreased while the vimentin level increased (P < 0.05), suggesting the occurrence of EMT. The AChE enzymatic activity decreased gradually. The expression of acetylcholine receptor mRNA changed as follows (GBW11110K/GBW11126D: CHRM3 (↑↑), CHRM5 (↓↓), CHRNA5 (↓↓), CHRNA7 (↓↓), CHRNA9 (- ↑), CHRNB2 (- -). The addition of exogenous AChE recombinant protein could antagonize the damage effects caused by the coal particles to a certain extent. Conclusion: The coal particle exposure could induce the change of oxidative stress response, inflammatory response and EMT related markers, down-regulate the AChE enzymatic activity, and interfere the mRNA expression levels of AChRs in A549 cells. The addition of exogenous AChE recombinant protein could reverse the above effects to a certain extent.

[Meta-analysis on association between interleukin-6-174C/G and -634C/G polymorphisms and pneumoconiosis susceptibility].

OBJECTIVE: To explore the association between the interleukin-6-174 C/G and-634 C/G polymorphisms and pneumoconiosis susceptibility. METHODS: Taking pneumoconiosis, interleukin-6, and polymorphism as keywords, Chinese literatures were retrieved among the Sinomed, Wanfang Medicine, CNKI and VIP databases, and foreign language literatures were retrieved among the Pubmed, Embase, Cochrane Library and Web of Science databases. Taking pneumoconiosis, susceptibility, and interleukin-6 as keywords, Revman 5. 2 software was employed to combine the genetic effects and evaluate the quality of the included literatures. RESULTS: A total of seven literatures(containing nine case-control studies) were included, including 660 cases and 848 controls with IL-6-174 C/G polymorphism, and 344 cases and 362 controls with IL-6-634 C/G polymorphism. Meta-analysis shows that IL-6-174 C/G polymorphism is not associated with pneumoconiosis susceptibility(CC νs. CG+GG, OR=1. 05(95%CI 0. 76-1. 45), CG νs. GG+CC, OR=0. 79(95%CI 0. 40-1. 55), C νs. G, OR=0. 95(95% CI 0. 80-1. 14)), while IL-6-634 C/G polymorphism is associated with pneumoconiosis susceptibility(CC νs. CG+GG, OR=2. 12(95%CI 1. 56-2. 88), CG νs. GG+CC, OR=0. 40(95%CI 0. 27-0. 58), C νs. G, OR=1. 67(95%CI 1. 33-2. 11)). CONCLUSION: There exists an association between the IL-6-634 C/G polymorphism and pneumoconiosis susceptibility, while there isn't an association between the IL-6-174 C/G polymorphism and the susceptibility of pneumoconiosis. IL-6-634 C/C genotype is pneumoconiosis-susceptible genotype.

SAM targeting methylation by the methyl donor, a novel therapeutic strategy for antagonize PFOS transgenerational fertilitty toxicity.

DNA methylation have been suggested as possible mediators of long-term health effects of environmental stressors. This study aimed to evaluate the potential therapy of methylation of S-adenosyl-l-methionine (SAM) on PFOS induced trangeneral reproductive toxicity. In this study, postnatal 5d Sprague Dawley rats were randomly divided into four groups: control, PFOS, PFOS + SAM, and PFOS + Decitabine (DAC). The F0 rats were exposed to 5 mg/kg PFOS and SAM or DAC until PND60. The development of the offsprings were monitored without PFOS exposure. The fertility in F0, F1 rats, and change in F1 testes were observed. The results were as follows. The significant increase in F0 pregnancy rate, and survival rate in F1 offspring in PFOS + SAM relative to PFOS group were observed. Changes of birth weights and physical development in F1 offspring with SAM were approached as a corresponding variation of the control after the deparation period. No pregnant in F1 maternal rats in the PFOS and DAC groups were found, but pregnant in the SAM group. Significantly decrease in the percentage of abnormal seminiferous tubules and increase in expression of promyelocytic leukemia zinc finger (PLZF+) spermatogonial stem cells in F1 testis compared with the PFOS group. Taken together, Methyl donor SAM improve PLZF + spermatogonia stem cell proliferation, attenuate damage in testicular tissue structure, which subsequently improve the transgenerational growth retard and infertility induced by PFOS chronic stress.