[Protective effect of FAK inhibitor PF-562271 against human umbilical vein endothelial cell injury induced by aging platelets].

OBJECTIVE: To investigate the protective effect of PF-562271, a FAK inhibitor, against aging platelet-induced injury in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with vehicle, lipopolysaccharide (LPS), LPS+aging platelets, or LPS+aging platelets+PF-562271. The changes in protein expressions of FAK, pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay, and the level of reactive oxygen species (ROS) was detected with flow cytometry. The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test. RT-qPCR was used to analyze mRNA expressions of inflammatory factors, and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay. Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments. RESULTS: Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK, pFAK and PECAM-1, which were effectively lowered by addition of PF-562271 (P < 0.05). LPS and aged platelets obviously enhanced ROS production in the cells, which was inhibited by the addition of PF-562271 (P < 0.001). PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets (P < 0.01). The expressions of TNF-α, IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets, and were obviously lowered after treatment with PF-562271 (P < 0.05). Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells (P < 0.01). CONCLUSION: The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

The development of occupational exposure limits for chemical substances in China.

This paper presents a comprehensive review of the occupational exposure limits (OELs) of chemical substances in China. It provides historical background on the development of OELs in this country, with a complete list of traditionally adopted and newly developed OELs for chemicals in workplaces. The philosophical thoughts, the administrative system, the scientific protocols for setting and amending health standards, with emphasis on making health a basic criterion for setting health standards, strengthening epidemiological studies of the human population, integrating epidemiological and toxicological studies, considering technological and economical feasibilities, and making full use of literature information sources are discussed. Further perspectives with respect to practical issues of maximum allowable concentration and time-weighted average, selection of safety factors, and establishment of biological exposure limits are also considered, with the authors' contributions to a discussion on these topics.

Development of occupational hygiene standards in the People's Republic of China.

This article reviews the history and implementation of the development of occupational hygiene standard setting in the People's Republic of China. The author raises questions concerned with standard setting and gives examples of toxicants for which the scientific basis of revision is given. The principles and approaches used to set or revise hygiene standards in China are explained, and suggestions to help speed up the standard setting are also given. As a rule, field and epidemiologic surveys and the utilization of existing toxicologic information are emphasized. Repetitions of animal experimentation should be avoided.