Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Correlation between the deletion of phosphatase and tensin homolog gene on chromosome 10, syncytin-1 and the damage of maternal endothelium and trophoblast in preeclampsia placenta / 中国综合临床

Objective:To study the correlation between phosphatase and tensin homolog deleted on chromosome ten(PTEN), Syncytin-1 in preeclamptic placenta and maternal endothelial injury, trophoblast injury.Methods:From February 2015 to December 2017, 46 patients diagnosed as preeclampsia and delivered in Xiaolan Hospital Affiliated to Southern Medical University and 80 pregnant women with normal delivery in the same period were selected.Before delivery, maternal peripheral blood was collected and the content of endothelial injury markers was determined; after delivery, the placenta was retained and the expression of PTEN, Syncytin-1, apoptosis gene and the contents of oxidative stress markers were measured.Results:The mRNA expression of PTEN in placental tissue of preeclampsia was significantly higher than that of normal placental tissue( t=32.797, P<0.000), and the mRNA expression of Syncytin-1 was significantly lower than that of normal placental tissue( t=28.506, P<0.001); the content of ET-1 and sFlt-1 in the blood circulation of the maternal body of preeclampsia was significantly higher than thsoe of normal pregnant women( t=39.884, 40.243; all P<0.000) and positively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=0.674, 0.596; P=0.004, 0.007), negatively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=-0.615, -0.637; P<0.009, 0.008); the content of NO, PGI2, VEGF and PLGF were significantly lower than thse of normal pregnant women( t=30.944, 27.404, 32.827, 26.644; all P<0.001) and negatively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=-0.648, -0.592, -0.537, -0.613; P=0.006, 0.009, 0.013, 0.007), positively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=0.632, 0.572, 0.537, 0.654; P<0.010, 0.013, 0.015, 0.009); The contents of NOX4, MDA, 8-OHdG and the mRNA expression of Fas, FasL, Bax, GRP78, CHOP, Caspase-3 in placental tissue of preeclampsia was significantly higher than that of normal placental tissue( t=27.714, 27.704, 26.786, 27.964, 22.622, 25.496, 25.893, 30.837, 28.975; all P<0.001) and positively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=0.703, 0.651, 0.593, 0.628, 0.449, 0.552, 0.612, 0.569, 0.502; P<0.003, 0.007, 0.004, 0.006, 0.016, 0.010, 0.006, 0.012, 0.018), negatively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=-0.615, -0.714, -0.577, -0.548, -0.512, -0.585, -0.619, -0.495, -0.662; P<0.009, 0.001, 0.013, 0.015, 0.018, 0.011, 0.009, 0.023, 0.003); The contents of PrxII, PrxIII, SOD and mRNA expression of Bcl-2 in placental tissue of preeclampsia was significantly lower than that of normal placental tissue( t=26.115, 23.502, 17.194; all P<0.000) and negatively correlated with the mRNA expression of PTEN in placenta(correlation coefficien t=-0.713, -0.657, -0.591, -0.642; P<0.001, 0.006, 0.009, 0.007), positively correlated with the mRNA expression of Syncytin-1 in placenta(correlation coefficien t=0.562, 0.711, 0.682, 0.608, P<0.013, <0.001, 0.002, 0.008). Conclusion:The high expression of PTEN and the low expression of syncytin-1 in placenta of preeclampsia can aggravate the damage of endothelium and trophoblast.

Expression and characterization of a novel halohydrin dehalogenase from Tistrella mobilis KA081020-065 / 生物工程学报

Halohydrin dehalogenase is of great significance for biodegradation of the chlorinated pollutants, and also serves as an important biocatalyst in the synthesis of chiral pharmaceutical intermediates. A putative halohydrin dehalogenase (HheTM) gene from Tistrella mobilis KA081020-065 was cloned and over-expressed in Escherichia coli BL21 (DE3). The recombinant enzyme was purified by Ni-NTA column and characterized. Gel filtration and SDS-PAGE analysis showed that the native form of HheTM was a tetramer. It exhibited the highest activity at 50 degrees C. The nature and pH of the buffer had a great effect on its activity. The enzyme maintained high stability under the alkaline conditions and below 30 degrees C. HheTM catalyzed the transformation of ethyl(S)-4-chloro-3-hydroxybutyrate in the presence of cyanide, to give ethyl (R)-4-cyano-3-hydroxybutyrate, a key intermediate for the synthesis of atorvastatin.

Vitro antitumor activity and synthesis of the key intermediate of bakuchiol / 药学学报

The in vitro antitumor activity of bakuchiol was exploited, compared with tamoxifen. The result of biological activities showed that bakuchiol could inhibit human breast cancer and the IC50 values were 2.89 x 10(-5) mol L(-1) and 8.29 x 10(-3) mol L(-1) against the cells line T-47D and MDA-MB-231 respectively. On the other hand, the key intermediate to synthesize bakuchiol was obtained by the method of Ireland-Claisen rearrangement. Comparing with traditional Claisen rearrangement, the reaction conditions are milder and the reaction reagents are safer.