Advances in in vitro and in vivo models for Listeria monocytogenes placental infection / 生物工程学报

Listeria monocytogenes is recognized as a significant foodborne pathogen, capable of causing listeriosis in humans, which is a global public health concern. This pathogen is particularly dangerous for pregnant women, as it can lead to invasive listeriosis in fetuses and neonates, posing a significant threat to both maternal and fetal health. Therefore, establishing suitable in vitro and in vivo models for L. monocytogenes placenta infection, as well as analyzing and exploring the infection process and its pathogenic mechanism, are important approaches to prevent and control L. monocytogenes infection in mothers and infants. In this study, we reviewed the in vitro and in vivo placental models used for studying the infection of L. monocytogenes in maternal and infant, summarized and discussed the advantages and limitations of each model, and explored the potential of in vitro cell models and organoids for the study of L. monocytogenes infection. This paper aims to support the study of the infection pathway and pathogenesis of listeriosis and provide scientific references for the prevention and control of L. monocytogenes infection.

Embryo-fetal development toxicity of carenoprazan hydrochloride / 中国药科大学学报

@#Carenoprazan has the similar structure and mechanism with the potassium-competitive blocker vonoprazan. Howerver, its safety during the pregnancy remains uncertain. To study the embryo-fetal development toxicity and toxicokinetics of carenoprazan hydrochloride via oral administration, time-mated Sprague-Dawley rats were divided into 5 groups, treated with normal saline, cyclophosphamide for injection(3. 8 mg/kg), and carenoprazan hydrochloride(20, 60, 200 mg/kg), respectively. Administrated orally from gestation day(GD)6 - 15. At the termination(GD 20), pregnant dams were sacrificed, and concentrations of carenoprazan hydrochloride as well as its metabolite in plasma and issues of both maternal and fetus were examined. As a result, the body weight gain of maternal in both high(200 mg/kg)and medium(60 mg/kg)dose as well as the food consumption of high-dose were decreased during GD 10-16. At the high dose group, decrease of crown rump length of fetuses were significant. Also, skeletal malformation/variations of fetus increased obviously at both high- and medium- dosage. The toxcicokinetics of carenoprazan hydrochloride are linear after single treatment between 20-200 mg/kg. The placental barrier was penetrated by carenoprazan hydrochloride and metabolite, and the distribution of metabolite in organs were similar in both maternal and fetus, with the highest concentration in livers. Therefore might resulted in the development toxicity. The No Observed Adverse Effect Level(NOAEL)of carenoprazan hydrochloride for both maternal and fetal was 20 mg/kg.

Evaluation of embryo toxicity of Shuanghuanglian based on human placental barrier model / 中国药理学与毒理学杂志

OBJECTIVE To evaluate the embryo toxicity of Shuanghuanglian (SHL) by the combination of a human placental barrier model and embryonic stem (ES) cell test model.METHODS A human placental barrier model was set up by placenta slice culture and Ussing chamber.SHL 0.2,0.4,0.8,1.6,3.2,6.4 and 12.8 g· L-1 was added into the maternal side of the human placental model,respectively.All the media was collected respectively from the matemal side and fetal side 60 min later and taken as the SHL containing medium.ES cells (D3 line) and embryonic fibroblast cells (BALB/c 3T3) were cultured with the SHL containing medium respectively from the maternal side and the fetal side for 10 d.Cell viability was detected by MTT assay,and 50％ survival inhibitory ratio of ES and 3T3 cells by SHL was calculated.ES cells were incubated with the SHL containing medium from the matemal side or fetal side when they differentiated to cardiac myoblasts using hanging drop-suspension-attachment method.Messenger RNA of myosin heavy chain genes (β-MHC) was detected by Q-PCR for differentiation ratio,and 50％ differentiation inhibitory ratio of ES cells by SHL was calculated.A statistics formula was used for prediction of SHL embryotoxicity potential.RESULTS The IC50 of SHL in the matemal side of the human placental model for 3T3 cell survival,ES cell survival and ES differentiation was 1.97,0.84 and 0.48 g· L-1,respectively.According to the criteria for embryo toxicity evaluation,SHL had weak embryo toxicity.However,the IC50 of SHL in the fetal side of the human placental model for 3T3 cell survival,ES cell survival and ES differentiation was 3.19,2.57 and 0.95 g· L-1,respectively.According to the criteria for embryo toxicity evaluation,the supernatant containing SHL that went through the placental barrier had no embryo toxicity.CONCLUSION SHL is safe in the test concentration range during pregnancy.It is more scientific to evaluate embryo toxicity of drugs by ES cell test with the samples obtained through the placental barrier during pregnancy.

Identification of P-Glycoprotein and Transport Mechanism of Paclitaxel in Syncytiotrophoblast Cells

When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with Km of 168 microM and 371 microM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [3H]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [3H]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.

Identification of P-Glycoprotein and Transport Mechanism of Paclitaxel in Syncytiotrophoblast Cells

When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with Km of 168 microM and 371 microM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [3H]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [3H]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.