NIK-mediated reactivation of SIX2 enhanced the CSC-like traits of hepatocellular carcinoma cells through suppressing ubiquitin-proteasome system.

The critical roles of NF-κB Inducing Kinase (NIK) in tumor progression have been elucidated in various tumors; however, its effects on hepatocellular carcinoma (HCC) progression are still confusing. Here, we found that NIK level was upregulated in HCC tissues compared to that of normal tissues, and positively correlated with the levels of cancer stem cell (CSC) markers. Then we established HCC cells with NIK-stable knockdown and found that NIK knockdown suppressed the CSC-like traits of HCC cells through in vivo and in vitro experiments. Mechanistically, we revealed that SIX2 protein level, but not its mRNA level, was significantly reduced in HCC cells with NIK knockdown, which was rescued by MG132 treatment. Furthermore, NIK knockdown promoted the ubiquitination level of SIX2 and decreased its protein stability. Moreover, Six2 overexpression partially reversed the inhibition of NIK knockdown on the CSC-like traits of HCC cells. This study identified a novel NIK/SIX2 axis conferring HCC stemness.

Influence of Guizhi Jia Longgu Mulitang on Expression of IL-10 and TNF-α in Insomnia Rats with Sensory Dysfunction Dominated by Lung / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Guizhi Jia Longgu Mulitang on the expression difference of interleukin-10 （IL-10） and tumor necrosis factor -α （TNF-α） in related organs of insomnia rats with sensory dysfunction dominated by lung and study the mechanism of Guizhi Jia Longgu Mulitang in improving insomnia. MethodSD rats were randomly divided into the blank group， model group， western medicine group， and traditional Chinese medicine （TCM） group， with 10 rats in each group. The rats were deprived of sleep by shallow water environment method in a long platform， and the modeling lasted for 42 d. The blank group and model group were given 0.05 mL·kg-1 normal saline by gavage， and the western medicine group and TCM group were given drugs during modeling. To be specific， the western medicine group was given 0.105 mg·kg-1 dexzopiclone tablet by gavage， while the TCM group was given 7 600 mg·kg-1 Guizhi Jia Longgu Mulitang by gavage， both lasting for 28 days. After successful modeling， the Morris water maze experiment was performed on the 42nd day to detect the motion and spatial memory ability of rats. The levels of IL-10 and TNF-α in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expression of IL-10 and TNF-α in the lung and brain tissue of rats was detected by Western blot. The levels of IL-10 and TNF-α in the lung and brain tissue of rats were detected by immunohistochemistry. ResultCompared with the blank group， the sleep stages non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) of the model group were significantly shortened （P<0.5， P<0.01）， and the wake stage was significantly increased （P<0.01）. The total time and distance of platform exploration were significantly increased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly decreased （P<0.01）. ELISA results showed that the serum IL-10 level was significantly decreased （P<0.01）， and TNF-α level was significantly increased （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain and lung tissue of rats was significantly decreased （P<0.01）， and the protein expression of TNF-α was significantly increased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in the brain and lung tissue of rats was significantly decreased （P<0.01）， and that of TNF-α was significantly increased （P<0.01）. Compared with the model group， the NREM stage and REM stage of the western medicine group and the TCM group were significantly increased （P<0.5， P<0.01）， and the wake stage was shortened （P<0.5）. The total time and distance of platform exploration were significantly decreased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly increased （P<0.05， P<0.01）. The serum IL-10 level was significantly increased （P<0.01）， and the serum TNF-α level was significantly decreased according to the ELISA results （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.01）， and the protein expression of TNF-α was significantly decreased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.05， P<0.01）， and the expression of TNF-α was significantly decreased （P<0.05， P<0.01）. ConclusionGuizhi Jia Longgu Mulitang can improve the expression of IL-10 and TNF-α in brain and lung tissue of insomnia rats with sensory dysfunction dominated by lung， prolong sleep time， and then improve insomnia. The mechanism may be related to improving the expression level of inflammatory factors.

Curcumin reverses hepatocyte growth factor-induced resistance to gefitinib in PC9 lung cancer cells / 中国病理生理杂志

AIM:To explore the molecular mechanism through which curcumin reverses hepatocyte growth factor (HGF)-induced resistance to gefitinib in lung cancer cells.METHODS:The methods of MTT assay, wound healing assay and Western blot were used to observe the effects of HGF, curcumin and gefitinib on the migration, drug susceptibility, epithelial-mesenchymal transition, and related signaling pathways in the PC9 lung cancer cells.RESULTS:HGF reduced susceptibility of the PC9 cells to gefitinib, and curcumin significantly reversed HGF-induced resistance to gefitinib.HGF induced migration and epihelial-mesenchymal transition, and promoted c-Met/AKT/mTOR pathway activation in the PC9 cells.Gefitinib alone did not prevent the above activities.However, combined with curcumin, gefitinib prevented the above activities.CONCLUSION:Curcumin reverses HGF-induced resistance of the PC9 cells to gefitinib by preventing epithelial-mesenchymal transition and inhibiting c-Met/AKT/mTOR activation.

Role of STAT3 in the pathogenesis of acute viral myocarditis in mice / 重庆医科大学学报

Objective:To investigate the role of STAT3 in the pathogenesis of acute viral myocarditis(VCM)in mice and its possible mechanism.Methods:Acute VCM mice models were established forty-five mice were randomly divided into blind control group (n=10),virus-infection control group(n=15),RPMintervention group(n=20).In RPM intervention group,RPM was given to mice intraperitoneally once a day with general dosage of 0.4 mg(/kg?d)at 24 hours before infected with coxsackie virus B3,mice of virus-infection control group were given the same volume of Dulbcco's Modifed Eagle Medium and virus.Blind control group was only given the same volume of Dulbcco's Modifed Eagle Medium,but not infected coxsackie virus B3.Twelve days later,the general condition and survival rate of mice were observed and then all experimental mice were sacrificed patholog and detecting CVB3 virus titer in myocardium. And double-sandwich ELISA was used to detect the levels of IFN-?,and TNF-?in the serum.Results:The pathological changes of myocardium of the mice in RPM intervention displayed more seriously than the mice with acute VMC and both the cytokines expressions in the serum of RPM intervention group were higher than those of the acute VMC group,but there was no significant difference in the virus titer between the two groups.Conclusions:The activation of STAT3 can somehow protect myocardial tissues during the incidence of viral myocarditis in mice to inhibit its activation and improve the sensibility of mice to CVB3,although the activation of STAT3 cannot affect CVB3 virus replication,it can inhibit the over-expression of IFN-?and TNF-?to weaken myocardial damage.