1.Advances of toxicology and toxicologic mechanism of phthalate esters
Lei LI ; Naining SONG ; Haishan LI ; Wenchao AI ; Huiming CHEN
Chinese Journal of Pharmacology and Toxicology 2014;(3):468-474
Phthalate esters (PAEs)are by far the most widely used plasticisers and are categorized as high and low,depending on their molecular weight.Because of their extensive use,humans are most likely exposed to PAEs in the workplace and home environment through direct as well as indirect sources.Injection,inhalation,intravenous injection and skin absorption are potential pathways of expo-sure.With respect to health effects,phthalates are often classified as endocrine disruptors because of their ability to interfere with the endocrine syste m in the body.Furthermore,PAEs possess reproductive toxicity because of their influence on development of the reproductive system in infancy and development and differentiation of germ cells in adults.PAEs promote pathogenesis and development of liver cancer by activating peroxisome proliferator-activated receptor (PPAR)and DNA methylation.In addition, PAEs,which inhibit the i mmune functions of macrophages and pro mote hypersensitive response,pos-sess immunotoxicity.PAEs are also carcinogens that promote pathogenesis and development of cancers including breast,ovarian and so me other cancers.
2.Effect of aerobic exercise on enteric nervous injury in rats exposed to malathion
Haishan LI ; Lingfang KONG ; Songtao WANG ; Erlei ZHANG ; Wenchao AI ; Wenping XIE ; Huiming CHEN
Chinese Journal of Pharmacology and Toxicology 2014;(2):238-242
OBJECTIVE To investigate the effects of aerobic exercise on enteric nervous injury in rats exposed to malathion.METHODS Adult male Wistar rats were treated with non-load swi mming every other day,three ti mes a week,each one hour,for six weeks.Before exercise,the rats were trea-ted with malathion 100 mg·kg -1·d -1 by oral gavage,six days a week,for six weeks.The activities of seru m acetylcholinesterase(AChE)and butyrocholinesterase(BuChE)were determined.In addition,the s mall intestinal propulsion indexes were measured.Also,the distribution of nerve plexus in ileu m was observed.The i mmunohistoche mical method was used to measure the levels of protein gene-related petide 9.5 (PGP9.5),substance P (SP),and vasoactive intestinal peptide (VIP).RESULTS Co m-pared with normal control,malathion exposure decreased the activities of seru m AChE and BuChE (P<0.01 ),increased the s mall intestinal propulsion indexes (P <0.05).In addition,the levels of PGP9.5 decreased (P<0.05).At the sa me ti me,the levels of SP increased,and the levels of VIP decreased (P<0.05).Aerobic exercise did not change the activites of cholinesterases,but decreased s mall intes-tinal propulsion indexes,increased the levels of PGP9.5,decreased the levels of SP,and increased the levels of VIP.Co mpared with the malathion exposure only,the rats in malathion ad ministration co mbined with aerobic exercise group de monstrated much lower activites of cholinesterase (P <0.01 ),and the s mall intestinal propulsion indexes decreased fro m (89 ±4)% to (79 ±5)%(P <0.01 ).Moreover,the levels of PGP9.5 increased fro m 0.012 ±0.003 to 0.029 ±0.015 (P <0.01 ).At the sa me ti me,the levels of SP decreased fro m0.174 ±0.067 to 0.1 10 ±0.057(P<0.05),and the levels of VIP increased fro m 0.0076 ±0.0029 to 0.01 1 1 ±0.0047 (P <0.05).The levels of above para meters were sa me or close to those of the normal control.CONCLUSION Malathion exposure induced disorders of enteric nervous syste m in rats,and the aerobic exercise abated the toxic response in enteric nervous syste m of malathion exposure rats.However,these effects were not mediated through recovery of cholinesterases inhibition.
3.Activin A and BMP-4 induce cardiomyocyte-like cells differentiation of human amniotic epithelial cells.
Xiaoyu HAN ; Qi WAN ; Wenchao WU ; Ai ZHENG ; Liang LI ; Xiaojing LIU
Journal of Biomedical Engineering 2011;28(6):1217-1222
Amniotic epithelial cells (AECs) have been expected to be a good cell source for stem cell-based cardiac repair. Activin A signaling is required for cardiac differentiation in human embryonic stem cells (ESCs), and bone morphogenetic protein-4 (BMP-4) is an important regulator that controls stem cell fates. Previous study has established an efficient protocol to generate cardiomyocytes from human ESCs via induction with Activin A and BMP-4. The aim of present study was to test the hypothesis that Activin A and BMP-4 could also induce AECs to differentiate into cardiomyocytes in vitro. Human AECs (hAECs) were isolated from human term placenta by trypsin digestion according to the previous reports. Freshly isolated hAECs were examined to detect the expression of cytokeratin 19 by immunocytochemistry. High-density undifferentiated hAECs at passage 1 were sequential treated with 100 ng/ ml human recombinant Actvin A and 10 ng/ml BMP-4. The expression of cardiac-specific genes was examined before and after in vitro induction of cellular differentiation. Freshly isolated hAEC could express cytokeratin 19, the specific marker of epithelial cells. The data showed that hAECs treated with Activin A and BMP-4 were able to express cardiac-specific genes, including Nkx2.5 and alpha-actinin. Our results demonstrated that Activin A and BMP-4 could induce cardiomyocyte differentiation of hAECs, which might be a novel approach to induce differentiation of AECs into cardiomyocytes-like cells.
Activins
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pharmacology
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Amnion
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cytology
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Bone Morphogenetic Protein 4
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pharmacology
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Cell Culture Techniques
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Cell Differentiation
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drug effects
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Cells, Cultured
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Epithelial Cells
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cytology
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Humans
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Myocytes, Cardiac
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cytology
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Recombinant Proteins
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pharmacology
4.Advances in research and application of ionizing radiation biomarkers
Hongling OU ; Wenchao AI ; Yan WANG ; Yingying MA ; Lei SHI ; Qiaoyun ZHANG ; Xiujun SONG ; Xinru WANG
Chinese Journal of Pharmacology and Toxicology 2024;38(1):70-78
Exposure to ionizing radiation intervenes in genomic stability and gene expression,resulting in the disruption of normal metabolic processes in cells and organs by causing complex biolog-ical responses.Altered genomic variations,gene expression and metabolite concentrations in blood or tissue samples reflect systemic radiation damage.With the application of new techniques and exten-sive study on the mechanisms for ionizing radiation damage,related indicators such as chromosomal variation,gene expression,lipid and metabolism are being recognized and promise to be the markers for early diagnosis and prognosis of radiation exposure.Therefore,this article reviews recent progress in and potential applications of biomarkers related to ionizing radiation injury.