The potential role of the prolyl isomerase Pin1 during blastocyst implantation and uterine decidualization in mice.

During early pregnancy in mice, the establishment of uterine receptivity and endometrial decidualization require the extensive proliferation and differentiation of endometrial epithelial cells or stromal cells. Pin1 has been suggested to act as a molecular 'timer' of the cell cycle and is involved in the regulation of cellular proliferation and differentiation by binding many cell-cycle regulatory proteins. However, its physiological role during early pregnancy is still not fully understood. Here, we employed immunohistochemistry to determine the spatiotemporal pattern of Pin1 expression during early pregnancy. We found that Pin1 was mainly localized in subluminal stromal cells on day 4, in the decidual zone on days 5 to 8 of pregnancy and in artificial decidualization. Using a uterine stromal cell culture system, we found that progesterone, but not estrogen, induced the expression of Pin1 in a progesterone receptor-dependent manner. Inhibition of Pin1 in the uterus leads to impaired embryo implantation and decidualization in mice. Notably, a decrease in Pin1 activation affected the functional execution of several implantation- or decidualization-related factors. These findings provide new evidence for a previously unknown function of Pin1 in mediating embryo implantation and decidualization during successful pregnancy establishment and maintenance.

ATPR induces acute promyelocytic leukemia cells differentiation and growth arrest by blockade of SHP2/Rho/ROCK1 pathway.

Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia with a unique chromosome translocation t (15;17), commonly complicated by a complex coagulopathy. 4-Amino-2-trifuoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, was synthesized by our group and known to possess obvious biological anti-tumor activities. It has previously been shown that ATPR could induce differentiation and inhibit proliferation of APL cells, although the mechanism responsible for this effect was not well understood. In this study, we demonstrated that ATPR remarkably inhibited the expression and activity of SHP2. Further experiments showed silencing SHP2 or using SHP2 inhibition (SHP099) enhanced the effect of ATPR on cell proliferation and maturation. In addition, we also demonstrated that Rho/ROCK1 might be regulated by SHP2. Using Y-27632, a ROCK inhibitor, further proved that ROCK1 played an important role in ATPR-induced differentiation and proliferation suppression. In conclusion, the results from this study revealed that ATPR induced APL cells terminal differentiation and growth arrest by blockade of SHP2/Rho/ ROCK1 pathway.

Cyclophilin A plays an important role in embryo implantation through activating Stat3.

Embryo implantation is a crucial step for the successful establishment of mammalian pregnancy. Cyclophilin A (CYPA) is a ubiquitously expressed intracellular protein and is secreted in response to inflammatory stimuli to regulate diverse cellular functions. However, there are currently no reports about the role of CYPA in embryo implantation. Here, we examine the expression pattern of CYPA during mouse early pregnancy and explore the potential role of CYPA during implantation. CYPA is expressed in the subluminal stroma surrounding the implanting blastocyst on day 5 of pregnancy, but not at inter-implantation sites. In ovariectomized mice, estrogen and progesterone significantly stimulate CYPA expression. When pregnant mice are injected intraperitoneally with CYPA inhibitor, the numbers of implantation sites are significantly reduced. Using an in vitro stromal cell culture system, Ppia siRNA knockdown of CYPA and CYPA-specific inhibitor treatment partially inhibits levels of CD147, MMP3 and MMP9. Decreased CYPA expression also significantly inhibits Stat3 activity and expands estrogen responsiveness. Taken together, CYPA may play an important role during mouse embryo implantation.

[Establishment of a quality evaluation method for Angelica different processed products from genuine producing areas based on data mining].

The paper reports the development of a quality evaluation method for Angelica different processed products. The data of high-performance liquid chromatography, water, total ash and extract were analyzed with SPSS Clementine 11.0 software. Discriminant analysis (DA) established the classification model and parameter for Angelica different processed products. Fish's discriminant functions of Angelica different processed products were generated using 8 predictor variables selected from 59 indexes. The correct rate of discriminating back substitution is 96.7%. Angelica different processed products can be accurately and reliably recognized and validated with DA of SPSS Clementine 11.0 software.

[Quality control and discrimination of angelica different processed products based on HPLC fingerprints combined chemometrics methods].

OBJECTIVE: To establish a chemical fingerprint method for reorganizing and validating angelica different processed products. METHOD: A high-performance liquid chromatographic method was developed to establish the fingerprint. Principal component analysis, hierarchical cluster analysis and discriminate analysis were applied to study HPLC finger printing and chemical pattern reorganization. RESULT: There were difference of characteristic peaks and its relative peak area of HPLC fingerprints between different processed products. Fish's discriminate functions were generated by using six selected predictor variables, the tested samples of different processed products were classified with 100% accuracy, and discriminate analysis plots for the five groups were well-resolved. CONCLUSION: The developed HPLC finger print, combined with chemometrics, can accurately identify and validate angelica different processed products, the research provide theoretical basis for the processing mechanism and quality assess of angelica different processed products.

[Study on quality standard of oil-processed Radix Angelica sinensis].

OBJECTIVE: To establish the quality standard of oil-processed Radix Angelica sinensis. METHODS: Combined traditional identification, TLC and fingerprints of wine-processed Radix Angelica sinensis to control quality of oil-processed Radix Angelica sinensis. And referring to China Pharmacopoeia of 2005 edition, water, ash, and extract were also detected. RESULTS: The content of water, total ash, extract representatively was 7.30%, 8.70% and 50.9%. Eleven fingerprint peaks were defined, The eleven common peaks were appointed as fingerprint peaks by analyzing 14 representative samples, all the fingerprint peaks were quantified grounded on the peak of Ferulic acid. and quantified rested on the peak of ferulic acid. CONCLUSION: A multicomponent quantitative method for oil-processed Radix Angelica sinensis is established. The established method is feasible. The quality control standards of the oil-processed Radix Angelica sinensis is normative, systematic and accurate.

LncRNA NR-104098 Inhibits AML Proliferation and Induces Differentiation Through Repressing EZH2 Transcription by Interacting With E2F1.

Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Most lncRNAs have been proven to have biological and clinical significance in acute myeloid leukemia (AML), but further investigation remains necessary. In this study, we investigated lncRNA NR-104098 in AML and its specific mechanism. The microarray analysis was performed on NB4 cells. Based on the related analysis results, we identified that lncRNA NR-104098 is a suppressor gene that is significantly upregulated in AML cells. LncRNA NR-104098 could inhibit proliferation and induce differentiation in AML cells in vitro and also play main role in the mouse xenografts. Mechanically, it was confirmed that lncRNA NR-104098 may effectively inhibit EZH2 transcription by directly binding to E2F1 and recruiting E2F1 to the EZH2 promoter. In addition, ATPR can significantly increase the expression of lncRNA NR-104098, whereas knocking down NR104098 can inhibit the inhibitory effect of ATPR on the proliferation and induction differentiation of AML cells. Taken together, these results lead to deeper insight into the mechanism of ATPR-induced AML differentiation and prevent proliferation by inhibiting EZH2 on the transcriptional level.

Complement C4 induces regulatory T cells differentiation through dendritic cell in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Complement component 4 (C4) has be proved to play a role in pathogenesis of SLE. In the present study, we investigated the effect of C4 on T cells differentiation. METHODS: Thirty SLE patients were included in this study. CD4+ T cells were isolated from healthy subjects, and dendritic cells (DCs) were isolated from healthy subjects or SLE patients. C4 was supplemented to co-incubate with T cells and DCs. RESULTS: Serum C4 concentration was positively correlated with regulatory T cell (Treg) percentage (R(2) = 0.5907, p < 0.001) and TGFß concentration (R(2) = 0.5641, p < 0.001) in SLE patients. Different concentrations of C4 had no effect on T cells differentiation. Co-incubated T cells with DCs and C4 for 7 days, the Treg percentage and TGF-ß concentration were significantly elevated. In addition, pre-treated DCs (from healthy subjects or SLE patients) with C4 and then co-incubated with T cells, the increases of Treg percentage and TGF-ß concentration were also observed. CONCLUSION: C4 takes part in T cells differentiation to Treg cells via DCs.