Objective To investigate the relationship of STAT3 with expressions of MMP-2,MMP-9 and TIMP-1 and with epithelial-mesenchymal transition (EMT) in breast cancer cells,and to explore the clinical significances.Methods The mRNA of STAT3 and the protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 of breast cancer cells in 84 patients with breast cancer were determined by real-time RT-PCR technique and immunohistochemical method in paraffin-embedded specimensm respectively.Normal breast tissues adjacent to breast cancer were taken as controls.Results mRNA expression of STAT3 was significantly higher in breast cancer tissues than in controls (t=4.513,P＜ 0.001).Protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 were higher in breast cancer tissues than in controls (all P＜ 0.05).There were positive correlations between pSTAT3 expression and the expressions of MMP-2,MMP-9 and TIMP-1 in breast cancer tissues (all P＜0.05).The higher levels of pSTAT3 and MMP-2 were associated with poorer differentiation and more lymph node metastasis of breast cancer (both P＜0.05).The positive expression of MMP-9 was correlated with lymph node metastasis (P＜0.05),but not with histological grading (P＞0.05).The positive expression of TIMP-1 had no associations with histological grading and lymph node metastasis (both P＞0.05).There were no significant differences in the protein expressions level of pSTAT3,MMP-2,MMP-9 and TIMP-1 between different ages and different breast tumor sizes (all P＞0.05).Conclusions The increased expression of STAT3 in breast cancer cells is closely correlated with the increased expressions of MMP-2,MMP-9 and STAT3 inhibitor TIMP-1.The activation of STAT3 gene can mediate EMT by inducing the protein expressions of MMP-2,MMP-9,which promotes the invasion and metastasis of breast cancer.

Photoaffinity labeling is widely applied to demonstrate targets of small molecule ligands. In this paper, biotin photoaffinity labeled molecule with propargyl group 1 has been designed and synthesized, followed it's labeling of N2-acetyl-2'-O-propargyl guanosine 9 by "click chemistry". This technology presents delight development potential in labeling of second messenger cyclic nucleotide, antisense oligonucleotide or siRNA.

CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.

Objective: To investigate the expression of integrin β₃ in the endometrial implantation window of patients with cesarean scar and infertility, and its correlation with endometrial receptivity. Methods: A total of 40 patients with previous cesarean scar defect (PCSD) secondary infertility treated in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from April 2018 to December 2019 were enrolled as the observation group.The natural cycle of 40 normal women who were examined in our hospital at the same time were selected as the control group.The two groups were enrolled in the endometrium of the glandular epithelial cells for MMP-9, TIMP-1 and LIF immunohistochemical staining, and statistical analysis was performed.The serum E₂ and P levels of the implantation group were compared.The E₂/P ratio was measured and compared, and the expression level of integrin β₃ endometrial planting window was compared. Results: The MMP-9, TIMP-1 and LIF in the observation group [(175.31±56.36), (201.46±51.34), (209.23±45.23)] were significantly lower than those in the control group [(252.35±78.43), (257.23±74.13), (298.34±72.35)] (t=5.334, 5.766, 6.023, all P<0.05), but the E₂, P and E₂/P in the observation group [(515.31±56.36)pmol/L, (53.71±8.34)pmol/L, (13.23±5.23)] were higher than those in the control group[(352.35±78.43)pmol/L, (33.13±4.13)pmol/L, (8.17±2.91)] (t=7.334, 4.251, 3.241, all P<0.05). The level of beta 3 in the observation group (0.163±0.013) was significantly lower than that in the control group (0.253±0.031) (t=4.342, P<0.05). The thickness of endometrium in the observation group [(9.12±2.03)mm] was significantly thinner than that in the control group [(12.24±2.45)mm] (t=3.226, P<0.05). Conclusion The expression of integrin β₃ in the endometrial implantation window of patients with cesarean section scar infertility has a certain influence on endometrial receptivity.

OBJECTIVE: To explore the molecular pathological mechanism of liver metabolic disorder in severe spinal muscular atrophy (SMA). METHODS: The transgenic mice with type Ⅰ SMA (Smn^-/- SMN2^0tg/2tg) and littermate control mice (Smn^+/- SMN2^0tg/2tg) were observed for milk suckling behavior and body weight changes after birth. The mice with type Ⅰ SMA mice were given an intraperitoneal injection of 20% glucose solution or saline (15 μL/12 h), and their survival time was recorded. GO enrichment analysis was performed using the RNA-Seq data of the liver of type Ⅰ SMA and littermate control mice, and the results were verified using quantitative real-time PCR. Bisulfite sequencing was performed to examine CpG island methylation level in Fasn gene promoter region in the liver of the neonatal mice. RESULTS: The neonatal mice with type Ⅰ SMA showed normal milk suckling behavior but had lower body weight than the littermate control mice on the second day after birth. Intraperitoneal injection of glucose solution every 12 h significantly improved the median survival time of type Ⅰ SMA mice from 9±1.3 to 11± 1.5 days (P < 0.05). Analysis of the RNA-Seq data of the liver showed that the expression of the target genes of PPARα related to lipid metabolism and mitochondrial β oxidation were down-regulated in the liver of type Ⅰ SMA mice. Type Ⅰ SMA mice had higher methylation level of the Fasn promoter region in the liver than the littermate control mice (76.44% vs 58.67%). In primary cultures of hepatocytes from type Ⅰ SMA mice, treatment with 5-AzaC significantly up-regulated the expressions of the genes related to lipid metabolism by over 1 fold (P < 0.01). CONCLUSION Type Ⅰ SMA mice have liver metabolic disorder, and the down-regulation of the target genes of PPARα related to lipid and glucose metabolism due to persistent DNA methylation contributes to the progression of SMA.
Mice ; Animals ; PPAR alpha ; Liver Diseases ; Muscular Atrophy, Spinal/genetics* ; Mice, Transgenic ; Body Weight ; Glucose