Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation

肠道炎症与结直肠癌的发生发展密切相关，溃疡性肠炎（Ulcerative colitis）和克罗恩病(Crohn’s disease)患者发展为结直肠癌的风险明显高于正常人群。因此，研究炎症条件下结直肠癌的发生发展机制有望为预防和治疗肠炎相关结直肠癌提供重要的理论依据。细胞外基质蛋白Periostin与多种疾病的发生发展密切相关。大量的研究表明细胞外基质蛋白Periostin能够影响组织再生、炎症、纤维化以及肿瘤的发生发展。2020年1月21日，我校生命科学学院欧阳高亮教授课题组首次阐明了Periostin蛋白在炎症相关肿瘤发生发展中的功能及其作用机制，并可能为肠炎相关肠癌的治疗提供新的靶点。我校生命科学学院博士生马汉栋为该论文的第一作者，欧阳高亮教授和我校医学院刘迎福副教授为该论文的共同通讯作者。Periostin is a multifunctional extracellular matrix protein involved in various inflammatory diseases and tumor metastasis; however, evidence regarding whether and how periostin actively contributes to inflammation-associated tumorigenesis remains elusive. Here, we demonstrate that periostin deficiency significantly inhibits the occurrence of colorectal cancer in azoxymethane/dextran sulfate sodium-treated mice and in ApcMin/+ mice. Moreover, periostin deficiency attenuates the severity of colitis and reduces the proliferation of tumor cells. Mechanistically, stromal fibroblast-derived periostin activates FAK-Src kinases through integrin-mediated outside-in signaling, which results in the activation of YAP/TAZ and, subsequently, IL-6 expression in tumor cells. Conversely, IL-6 induces periostin expression in fibroblasts by activating STAT3, which ultimately facilitates colorectal tumor development. These findings provide the evidence that periostin promotes colorectal tumorigenesis, and identify periostin- and IL-6-mediated tumor-stroma interaction as a promising target for treating colitis-associated colorectal cancer.We thank Prof. Bin Zhao for providing pCMV5-FLAG-YAP WT and pCMV5-FLAG-YAP 5SA plasmids. We thank Prof. Yongyou Zhang for providing technical support. This work was supported by grants from the National Natural Science Foundation of China (81572598, 81772616, and 81972748), the Natural Science Foundation of Fujian Province of China (2019J02002), and the Health-Education Joint Research Program of Fujian Province (WKJ2016-2-16). 该研究工作获得了国家自然科学基金、福建省自然科学基金等资助

丹参活性成分靶点分子网络的生物信息学预测

目的:采用整合生物信息学方法预测丹参治疗心血管疾病的潜在机制。方法:从PubChem数据库中搜索丹参靶标蛋白,从NCBI数据库中搜索心血管疾病相关基因,利用IPA比较、分析搜索结果,预测丹参治疗心血管疾病的交互作用分子网络。结果:丹参治疗心血管疾病的靶标蛋白主要有FASN、 PAFAH1B2、PLA2G7、PAFAH1B3和IL-1β,这些蛋白主要涉及LXR/RXR活化、动脉粥样硬化、肝纤维化/肝星形细胞活化、急性反应期信号、FXR/RXR活化等信号传导通路;交互作用分子网络主要涉及细胞运动、免疫细胞运输、血液系统发育,参与DNA的复制、重组和修复等。结论:预测了丹参治疗心血管疾病的几个蛋白质靶点以及参与的信号途径;整合生物信息学方法可以用于分析小分子化学成分的作用机制

甲醇耦合的烷烃催化转化反应耦合效应评价方法及装置

一种甲醇耦合的烷烃催化转化反应的耦合效应评价方法，用于测定甲醇及其脱水转化反应产物对烷烃催化转化的耦合效应；主要过程是：通过质量流量计来控制不同流速载气流过含有烷烃或甲醇饱和发生器而携带出原料蒸汽，将蒸汽以脉冲方式进入反应器，获得不同接触时间条件下甲醇耦合烷烃催化转化的反应转化率和烷烃单独催化转化的反应转化率，并根据甲醇耦合烷烃催化转化的反应转化率和烷烃单独催化转化的反应转化率分别计算出上述两种催化转化的反应速率，甲醇耦合烷烃催化转化的反应速率与烷烃单独催化转化的反应速率之比为甲醇耦合的烷烃催化转化反应的耦合效应。带填

Clinical significance of S100A2 expression in gastric cancer

National Natural Science Funds of China [81101764]; Fundamental Research Funds for the Central Universities [2010121104]; Natural Science Foundation of Fujian Province of China [2011 J05099]Gastric carcinoma (GC) is one of the most common malignancies worldwide. To identify the candidate carcinoma-related biomarker in GC, comparative proteome technique was performed in resected GC tissues and matched adjacent non-cancerous gastric tissues (ANGT). As a result, S100A2 was successfully identified to be down-regulated significantly in GC compared with ANGT. Western blot analysis validated decreased expression of S100A2, and its expression level was related with the degree of tumor differentiation and status of lymph node metastasis in GC. Furthermore, immunohistochemistry analysis showed S100A2 down-expression was significantly associated with poor differentiation (P < 0.05), advanced depth of invasion (P < 0.05) and lymph node metastasis (P < 0.05) in GC. Kaplan-Meier curves showed that the relapse-free probability and the overall survival rate were significantly decreased with S100A2 expression decreasing (P < 0.05). Cox regression analysis indicated S100A2 down-expression was a negative independent prognostic biomarker for GC. A supplement of S100A2 protein by S100A2 expression vector significantly decreased the number of invaded cancer cells MGC-803. However, knockdown of S100A2 expression by siRNA interference compromised the invasion ability of MGC-803 cells. Moreover, S100A2 negatively regulated MEK/ERK signaling pathway, and activation of this signaling pathway by S100A2 down-regulation increased in vitro invasion of MGC-803 cells. In conclusion, this study demonstrated the clinical significance of S100A2 expression in GC, and loss of S100A2 expression contributes to GC development and progression. Therefore, the determination of S100A2 expression levels contributes to predict the outcome of GC patients

Identification of annexin A1 as a proinvasive and prognostic factor for lung adenocarcinoma

National Key Basic Research Program of China [2001CB510207]; Fundamental Research Funds for the Central Universities [2010 121104]; Ministry of Education of China [2002-48]Metastasis is the most common cause of death in lung cancer patients and is a major obstacle to the successful treatment. To discover novel metastasis-related proteins in lung adenorcinoma (AdC), quantitative proteomic analysis was performed between primary lung AdC tissues with (LNM AdC) and without lymph node metastasis (non-LNM AdC). In this study, annexin A1 was identified to be significantly up-regulated in LNM AdC compared with non-LNM AdC. Immunohistochemistry showed that annexin A1 over-expression was frequently observed in LNM AdCs and matched lymph node metastases compared with non-LNM AdCs. Annexin A1 over-expression was significantly associated with advanced clinical stage (P < 0.05) and lymph node metastasis (P < 0.05) and increased relapse rate (P < 0.05) and decreased overall survival (P < 0.05) in lung AdCs. Cox regression analysis indicated annexin A1 over-expression was an independent prognostic factor. Furthermore, suppression of annexin A1 expression by siRNA interference significantly inhibited the invasion ability of lung adenocarcinoma cell A549 in vitro. In conclusion, annexin A1 expression correlated with tumor stage, lymph node metastasis, relapse, and patient survival. Annexin A1 is proposed to function importantly in the progression of lung AdC

Prognostic significance of annexin II expression in non-small cell lung cancer

National Key Basic Research Program of China [2001CB510207]; National Natural Science Funds of China [81101764]; Fundamental Research Funds for the Central Universities [2010121104]; Natural Science Foundation of Fujian Province of China [2011J05099]To discover common metastasis-related and prognostic markers in lung squamous carcinoma (LSC) and lung adenocarcinoma (AdC), two forms of non-small cell lung cancer (NSCLC). Quantitative proteomic analysis was performed between primary cancer tissues and matched lymph node metastatic tissues in LSC and AdC, respectively. Immunohistochemistry and statistic analysis were performed to investigate prognostic significance of metastasis-related protein annexin II expression in LSC and AdC. Both in LSC and AdC, elevated expression of annexin II was identified in lymph node metastatic lung cancers compared to corresponding primary lung cancers. Furthermore, immunohistochemical analysis of a bulk of clinical specimens indicated that annexin II over-expression was more frequently observed in matched lymph node metastatic tissues than corresponding primary cancer tissues. Statistical analysis showed that annexin II over-expression was significantly associated with advanced clinical stage (P < 0.05) and lymph node metastasis (P < 0.05) and increased relapse rate (P < 0.05) and decreased overall survival (P < 0.05) in both two subtypes of NSCLC. Cox regression analysis indicated that annexin II over-expression was an important prognostic factor in both LSC and AdC. Annexin II was identified as a common prognostic factor in both LSC and AdC

Methanol Conversion over HZSM-22: the reaction mechanism and the effect of olefins aromatics addition

Methanol to olefin (MTO) conversion was studied on a home-made pulse reaction system. Under proper reaction conditions, complete conversion of methanol into olefins can be achieved over HZSM-22, which was previously reported to fail in the conversion of methanol to olefins. 13C labelling experiments and the addition of olefins and aromatics all indicate that the methanol conversion followed hydrocarbon pool mechanism is prohibited over HZSM-22 and the olefins methylation and cracking mechanism predominantly occurs

Quantitative proteomic analysis identifying three annexins as lymph node metastasis-related proteins in lung adenocarcinoma

National Key Basic Research Program of China [2001CB510207]; Fundamental Research Funds for the Central Universities [2010121104]; Ministry of Education of China [2002-48]; Science and Technology Committee of Hunan, China [04XK1001-1, 05SK1004-1]; Public Health Bureau of Hunan Province, China [Z02-04]Lymph node status is a strong predictor of outcome for lung adenocarcinoma (AdC) patients. To explore novel potential protein markers for predicting lymph node metastasis of lung AdC, differential proteomic analysis on microdissected cancer cells from primary lung AdC and matched lymph node (LN) metastatic tissues by laser capture microdissection (LCM) was conducted using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Annexins including annexin-1, annexin-2 and annexin-3 were identified and found to be overexpressed in matched LN metastatic tissues compared to primary lung AdC. Furthermore, differential expression levels of the three annexins were evaluated in paraffin-embedded 188 primary lung AdC tissues and 65 matched positive lymph node specimens using immunohistochemistry. High expression of annexin-1, annexin-2, and annexin-3 was all frequently observed in matched positive lymph node tissues compared to primary lung AdC. In primary lung AdC, expression levels of the three annexins in primary lymph node-positive AdC tissues were higher than primary lymph node-negative AdC tissues. Multivariate logistic regression analysis indicated annexin-1, annexin-2, and annexin-3 were all significant risk factors for lymph node metastasis. Furthermore, statistical analysis indicated that the concomitant expression of annexin-1/annexin-2, annexin-1/annexin-3, or annexin-2/annexin-3 and combined expression of all three markers had stronger correlation with lymph node metastasis. Our results suggest that annexin-1, annexin-2, and annexin-3 are identified as potential biomarkers associated with lymph node metastasis in lung AdC