ANGPTL4 regulates CD163 expression and Kuppfer cell polarization induced cirrhosis via TLR4/NF-κB pathway.

Angiopoietin like 4 (ANGPTL4) has been proved to play an important role in lipid and glucose metabolism disorders and related cardiovascular diseases, but its role in the formation of cirrhosis still needs to be further explored. Therefore, the aim of this study was to investigate the role of ANGPTL4 in the development of liver cirrhosis and its mechanism, as well as its effect on Kupffer cell polarization and hepatic stellate cell activation. The ELISA and RT-qPCR assay were used to detect the content of ANGPTL4 in serum and mRNA expression in cells and tissues respectively. The expression of ANGPTL4, Arg1 and Mrc2 in Kupffer cells was measured by Western blot. The percentage of CD163+ and CD206+ cells was measured by flow cytometry. Mice cirrhosis model was established, and the expression of ANGPTL4 was interfered by injecting sh-ANGPTL4 lentiviral vector into caudal vein. The results revealed that ANGPTL4 was significantly up-regulated in liver cirrhosis patients and HBV induced liver injury cell models. Further studies found that interference with ANGPTL4 regulated CD163 and inhibited the polarization and proinflammatory effects of KCs，as well as inhibited the activation of hepatic stellate cells (HSCs) and fibrosis. More importantly, Interference with ANGPTL4 inhibits the progression of liver cirrhosis in mice. What's more, TLR4/NF-κB pathway was involved in the molecular mechanism of ANGPTL4 on Kupffer cells and hepatic stellate cells. It is suggested that the mechanism of sh-ANGPTL4 suppressing the polarization of KCs and the activation of hepatic stellate cells (HSCs) is to regulate the TLR4/NF-κB signaling pathways.

Ultimate Strength Study of Structural Bionic CFRP-Sinker Bolt Assemblies Subjected to Preload under Three-Point Bending.

Countersunk head bolted joints are one of the main approaches to joining carbon fiber-reinforced plastics, or CFRP. In this paper, the failure mode and damage evolution of CFRP countersunk bolt components under bending load are studied by imitating water bears, which are born as adult animals and have strong adaptability to life. Based on the Hashin failure criterion, we establish a 3D finite element failure prediction model of a CFRP-countersunk bolted assembly, benchmarked with the experiment. The analysis shows that the simulation results under specified parameters have a good correlation with the experimental results, and can better reflect the three-point bending failure and fracture of the CFRP-countersunk bolted assembly. Based on the specified parameter of the carbon lamina material change, we used the countersunk bolt preload to investigate the stress distribution near the counterbore zone, and to investigate the effect of bolt load on the three-point bending limit load. The results obtained using FEA calculations indicate that the stress distribution around the countersunk hole is related to the laminate direction. The bolt preloading force increasing reduces the load value at the initial damage, and the appropriate preload force will increase the ultimate load of the joint.

Investigation of CFRP-Countersunk Bolted Assembly Fatigue Damage under Three-Point Bending via Experimental and Numerical Analysis.

In this research, the fatigue damage behavior under three-point bending of a composite joint incorporating a single countersunk fastener is investigated. Firstly, a self-developed fatigue test system was set up to test the fatigue characteristics of CFRP-countersunk bolted assembly under the displacement amplitude cycles of 103 to 106 to study the formation and expansion rule of damage and cracks. It found two typical damage processes, both of which involve some formal interface damage between fiber and matrix. Based on the experiment, a finite element fatigue damage analysis on this assembly was carried out according to the Hashin failure criterion. The simulation result shows an identical fatigue damage location and fatigue life with the experimental phenomenon. Moreover, it predicted the final fatigue life of the specimen under 10 hz cyclic loading with 1 mm displacement and 10 Nm bolt preloading. This research provides guidance for the engineering fatigue issues of single-bolted joint composite connection structures and provides a reference for the corresponding technical specifications formulation.

LINC02389/miR-7-5p Regulated Cisplatin Resistance of Non-Small-Cell Lung Cancer via Promoting Oxidative Stress.

Background: Non-small-cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and cisplatin-based chemotherapy is the main treatment for NSCLC. However, cisplatin resistance of NSCLC cells is a major challenge for NSCLC treatment. Materials and Methods: qRT-PCR and Western blot were performed to detect the expression of LINC02389 and miR-7-5p in NSCLC tissues and cell lines. Cell counting kit-8 (CCK-8) assay and flow cytometry assay were applied to exam cell proliferation and apoptosis rate of NSCLC cells. The interaction between LINC02389 and miR-7-5p was verified by dual luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay. Additionally, cisplatin-resistant NSCLC cells were generated to assess the biological function of LINC02389 and miR-7-5p in cisplatin resistance of NSCLC. Results: LINC02389 was highly expressed in NSCLC tissues and was correlated with poor prognosis of NSCLC patients. Knockdown of LINC02389 inhibited cell proliferation and promoted cell apoptosis of NSCLC, whereas miR-7-5p knockdown exerted the opposite effects. Moreover, LINC02389 negatively regulated the expression of miR-7-5p. In addition, LINC02389 was overexpressed, yet miR-7-5p was downregulated in cisplatin-resistant NSCLC cells compared with their parental cells. Moreover, oxidative stress biomarkers were overexpressed in cisplatin-resistant cells and were regulated by LINC02389. Besides, LINC02389 could reverse the inhibitory effect of cisplatin on NSCLC cells, which was partially reversed by attenuating the expression of miR-7-5p. Conclusion: Our research firstly demonstrated that lncRNA LINC02389 acted as an oncogene to promote progression, oxidative stress, and cisplatin resistance through sponging miR-7-5p and may provide therapeutic targets for NSCLC.

[Expression and significance of glypican-3 in colorectal cancer].

OBJECTIVE: To investigate the expression and significance of Glypican-3 in colorectal cancer. METHODS: Immunohistochemistry was used to detect the expression of Glypican-3 in 200 specimens of colorectal cancer and adjacent non-cancerous tissues resected during operation. RESULTS: Glypican-3 immunoreactivity was recognized in both the cytoplasm and cellular membrane. The Glypican-3 positive expression rate in the tumor samples was 66.0% (132/200), significantly higher than that in the adjacent nontumor tissues (24%, 48/200, P = 0.019). The Glypican-3 expression rate was significantly correlated with the carcinoma invasion (P = 0.023) and lymph node metastasis (P = 0.015), but not associated with gender, age, tumor size, and differentiation grade (all P > 0.05). CONCLUSION: Over-expression of Glypican-3 may play an important role in the genesis and development of colorectal cancer, and may be used as a new biological parameter in predicting invasion and metastasis of colorectal carcinoma.

Overexpression of NAD(P)H: Quinone Oxidoreductase 1 Inhibits Hepatocellular Carcinoma Cell Proliferation and Induced Apoptosis by Activating AMPK/PGC-1α Pathway.

Hepatocellular carcinoma (HCC) is the most common lethal malignancy and a leading cause of malignancy-associated death in many countries, but mainly in Asia. Expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is involved in the growth of various human cancers, including HCC. NQO1 is considered an inhibitor of cancers. The present study aimed to investigate the function and mechanism of NQO1 in HCC. In this study, we found that NQO1 overexpression decreased HCC cell SK-hep-1 and Hep3B cell proliferation and induced apoptosis. The apoptosis-associated gene Bax, Bcl-2, and caspase-3 expression was also measured, with western blot results showing that NQO1 overexpression inhibits Bcl-2 expression and promotes Bax and caspase-3 expression, whereas NQO1 silencing plays a contrasting role. In addition, NQO1 activated AMP-activated protein kinase (AMPK) and proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and the AMPK inhibitor compound C blocked NQO1-induced PGC-1α activation. Furthermore, the AMPK inhibitor compound C or PGC-1α siRNA partially abolished NQO1-induced cell apoptosis and proliferation inhibition in HCC cells. Taken together, our results demonstrate that NQO1 overexpression induces HCC cell apoptosis and proliferation inhibition through the AMPK/PGC-1α pathway.