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

In Vitro and In Vivo Study on the Effect of Lysosome-associated Protein Transmembrane 4 Beta on the Progression of Breast Cancer / 한국유방암학회지

PURPOSE: Although the effect of lysosome-associated protein transmembrane 4 beta (LAPTM4B) on the proliferation, migration, and invasion of breast cancer (BC) cells has already been studied, its specific role in BC progression is still elusive. Here, we evaluated the effect of different levels of LAPTM4B expression on the proliferation, invasion, adhesion, and tumor formation abilities of BC cells in vitro, as well as on breast tumor progression in vivo. METHODS: We investigated the influence of LAPTM4B expression on MCF-7 cell proliferation, invasion, adhesion, and tube formation abilities in vitro through its overexpression or knockdown and on breast tumor progression in vivo. RESULTS: Cell growth curves and colony formation assays showed that LAPTM4B promoted the proliferation of breast tumor cells. Cell cycle analysis results revealed that LAPTM4B promoted the entry of cells from the G1 into the S phase. Transwell invasion and cell extracellular matrix adhesion assays showed that LAPTM4B overexpression increased the invasion and adhesion capabilities of MCF-7 cells. More branches were observed in MCF-7 cells overexpressing LAPTM4B under an electron microscope. In comparison with LAPTM4B overexpression, LAPTM4B knockdown decreased the expression of vascular endothelial growth factor-A and significantly inhibited the vasculogenic tube formation ability of tumors. These results were also verified with western blot analysis. CONCLUSION: LAPTM4B promoted the proliferation of MCF-7 cells through the downregulation of p21 (WAF1/CIP1) and caspase-3, and induced cell invasion, adhesion, and angiogenesis through the upregulation of hypoxia-inducible factor 1 alpha, matrix metalloproteinase 2 (MMP2), and MMP9 expression. This specific role deems LAPTM4B as a potential therapeutic target for BC treatment.

Effects of early administration of high-dose rosuvastatin on coronary microvascular function and short-term outcome in patients treated with primary percutaneous coronary intervention for acute myocardial infarction / 中国医师进修杂志

Objective To investigate effects of early administration of high-dose rosuvastatin(40 mg) on coronary microvascular function and short-term outcome in patients treated with primary percutaneous coronary intervention (PCI) for acute myocardial infarction(AMI). Methods Ninety-four consequent AMI patients treated with primary PCI were divided into rosuvastatin group (50 patients) and control group (44 group). The infarct-related artery flow of epicardium was classified in compliance with the TIMI criteria. Myocardial and microvascular perfusion was assessed using the TMPG. The incidence of the MACE and the cytotoxicity and hepatotoxicity of rosuvastatin was respectively recorded in 30 d follow-up period. Results Either patients in the rosuvastatin group or in the control group showed better TMPG immediately after PCI (P<0.05), compared with that before treatment. However, the post-PCI TMPG of the rosuvastatin group was obviously much better than that of control group (P<0.05). Compared with that in control group, the 30-day composite MACE rate was lower in rosuvastatin group and in the TMPG 3 patients of rosuvastatin group:12.0%(6/50) vs. 34.1%(15/44), P<0.05;11.1%(3/27) vs. 42.9%(6/14). There was no cytotoxicity and hepatotoxicity in two groups. Conclusions Early administration of high-dose rosuvastatin (40 mg) can improve coronary microvascular function and short-term outcome in patients treated with primary PCI for AMI, and it is efficient and safety.