Interleukin-18 Synergism with Interleukin-2 in Cytotoxicity and NKG2D Expression of Human Natural Killer Cells

Qi, Yuan-Ying,Lu, Chao,Ju, Ying,Wang, Zi-E,Li, Yuan-Tang,Shen, Ya-Juan,Lu, Zhi-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Natural killer (NK) cells play an important role in anti-tumor immunity. Interleukin (IL)-18 is an immunoregulatory cytokine that induces potent NK cell-dependent anti-tumor responses when administrated with other cytokines. In this study, we explored the effects of combining IL-18 and IL-2 on NK cytotoxicity as well as expression levels of the NK cell receptor NKG2D in vitro. Freshly isolated PBMCs were incubated for 48 h with IL-18 and IL-2, then CD107a expression on $CD3^-CD56^+$ NK cells was determined by three-colour flow cytometry to evaluate the cytotoxicity of NK cells against human erythroleukemia K562 cells and human colon carcinoma HT29 cells. Flow cytometric analysis was also employed to determine NKG2D expression on NK cells. The combined use of IL-18 and IL-2 significantly increased CD107a expression on NK cells compared with using IL-18 or IL-2 alone, suggesting that the combination of these two cytokines exerted synergistic enhancement of NK cytotoxicity. IL-18 also enhanced NKG2D expression on NK cells when administered with IL-2. In addition, blockade of NKG2D signaling with NKG2D-blocking antibody attenuated the up-regulatory effect of combining IL-18 and IL-2 on NK cytolysis. Our data revealed that IL-18 synergized with IL-2 to dramatically enhance the cytolytic activity of human NK cells in a NKG2D-dependent manner. The results appear encouraging for the use of combined IL-18 and IL-2 in tumor immunotherapy.

Inhibition by Imatinib of Expression of O-glycan-related Glycosyltransferases and Tumor-associated Carbohydrate Antigens in the K562 Human Leukemia Cell Line

Sun, Qi-Chang,Liu, Mi-Bo,Shen, Hong-Jie,Jiang, Zhi,Xu, Lan,Gao, Li-Ping,Ni, Jian-Long,Wu, Shi-Liang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Objective: To study changes of tumor associated carbohydrate antigen (TACAs) expression and mRNA levels for tumor associated glycosyltransferases, and assess subcellular localizations of N-acetyl galactosyltransferases (GalNAc-Ts) in the K562 leukemia cell line after imatinib treatment. Methods: RT-PCR was performed to analyze the expression of glycosyltransferases which synthesize O-glycan in tumor-associated carbohydrate antigens (TCTAs). The expression of Tn antigen, T antigen and sialyl T antigen on K562 cell membranes was measured by flow cytometry after treatment with different concentrations of imatinib. Co-localization of GalNAc-Ts and ER (endoplasmic reticulum) was determined by confocal laser scanning microcopy. Results: Transcript expression levels of several glycosyltransferases related to TCTAs were decreased after imatinib ($0-0.3{\mu}M$) treatment. Expression of Tn antigen and T antigen was increased while that of sialyl T antigen was decreased. Co-localization of GalNAc-Ts and ER was reduced by $0.2{\mu}M$ of imatinib. Conclusion: Imatinib inhibited the expression of O-glycan related TACAs and several related glycosyltransferases, while decreasing the co-localization of GalNAc-Ts and ER and normalizing O-glycosylation in the K562 human leukemia cell.

Full-scale testing and modeling of the mechanical behavior of shield TBM tunnel joints

Wen-qi Ding,Yi-cheng Peng,Zhi-guo Yan,Bi-wei Shen,He-hua Zhu,Xin-xin Wei 국제구조공학회 2013 Structural Engineering and Mechanics, An Int'l Jou Vol.45 No.3

For shield TBM (Tunnel Boring Machine) tunnel lining, the segment joint is the most critical component for determining the mechanical response of the complete lining ring. To investigate the mechanical behavior of the segment joint in a water conveyance tunnel, which is different from the vehicle tunnel because of the external loads and the high internal water pressure during the tunnel’s service life, full-scale joint tests were conducted. The main advantage of the joint tests over previous ones was the definiteness of the loads applied to the joints using a unique testing facility and the acquisition of the mechanical behavior of actual joints. Furthermore, based on the test results and the theoretical analysis, a mechanical model of segment joints has been proposed, which consists of all important influencing factors,including the elastic-plastic behavior of concrete, the pre-tightening force of the bolts and the deformations of all joint components, i.e., concrete blocks, bolts and cast iron panels. Finally, the proposed mechanical model of segment joints has been verified by the aforementioned full-scale joint tests.

Preparation and Characterization of Anti-GP73 Monoclonal Antibodies and Development of Double-antibody Sandwich ELISA

Li, Qi-Wen,Chen, Hong-Bing,Li, Zhi-Yang,Shen, Peng,Qu, Li-Li,Gong, Lai-Ling,Xu, Hong-Pan,Pang, Lu,Si, Jin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. Materials and Methods: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. Results: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). Conclusions: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.

Full-scale testing and modeling of the mechanical behavior of shield TBM tunnel joints

Ding, Wen-Qi,Peng, Yi-Cheng,Yan, Zhi-Guo,Shen, Bi-Wei,Zhu, He-Hua,Wei, Xin-Xin Techno-Press 2013 Structural Engineering and Mechanics, An Int'l Jou Vol.45 No.3

For shield TBM (Tunnel Boring Machine) tunnel lining, the segment joint is the most critical component for determining the mechanical response of the complete lining ring. To investigate the mechanical behavior of the segment joint in a water conveyance tunnel, which is different from the vehicle tunnel because of the external loads and the high internal water pressure during the tunnel's service life, full-scale joint tests were conducted. The main advantage of the joint tests over previous ones was the definiteness of the loads applied to the joints using a unique testing facility and the acquisition of the mechanical behavior of actual joints. Furthermore, based on the test results and the theoretical analysis, a mechanical model of segment joints has been proposed, which consists of all important influencing factors, including the elastic-plastic behavior of concrete, the pre-tightening force of the bolts and the deformations of all joint components, i.e., concrete blocks, bolts and cast iron panels. Finally, the proposed mechanical model of segment joints has been verified by the aforementioned full-scale joint tests.

A System Performance Estimation Model for Cassandra Database

Bo-Qian Wang,Qi Yu,Xin Liu,Li Shen,Zhi-ying Wang 보안공학연구지원센터 2016 International Journal of Database Theory and Appli Vol.9 No.3

Cassandra database system is one of the universal databases. To achieve high performance, we should allocate memory space rationally according to actual demands. Otherwise, it will influence reading and writing performance. Actually, we always allocate memory space according to experience and repeated attempts which usually won’t give us the best answer. To solve this problem, firstly we analyze the reading and writing processing of the Cassandra database and find out the corresponding memory space which will influence system performance. Secondly, we build up a relationship model between system performance and memory allocation and name it as The Memory Model of Reading and Writing Performance. We have already applied the relationship model to real database servers to guide memory allocation and performance evaluation. Simulation results show that this memory model could well describe the quantization relationship of memory space and system performance.

Extracting Features of Human Knowledge Systems for Active Knowledge Management Systems

Yuan Miao,Robert Gay,Chee Kheong Siew,Zhi Qi Shen 한국지능정보시스템학회 2001 한국지능정보시스템학회 기타 간행물 Vol.- No.-

Mst1/2-ALK promotes NLRP3 inflammasome activation and cell apoptosis during Listeria monocytogenes infection

Aijiao Gao,Huixin Tang,Qian Zhang,Ruiqing Liu,Lin Wang,Yashan Liu,Zhi Qi,Yanna Shen 한국미생물학회 2021 The journal of microbiology Vol.59 No.7

Listeria monocytogenes (L. monocytogenes) is a Gram-positiveintracellular foodborne pathogen that causes severe diseases,such as meningitis and sepsis. The NLR family pyrindomain-containing 3 (NLRP3) inflammasome has been reportedto participate in host defense against pathogen infection. However, the exact molecular mechanisms underlyingNLRP3 inflammasome activation remain to be fully elucidated. In the present study, the roles of mammalian Ste20-like kinases 1/2 (Mst1/2) and Anaplastic Lymphoma Kinase(ALK) in the activation of the NLRP3 inflammasome inducedby L. monocytogenes infection were investigated. Theexpression levels of Mst1/2, phospho (p)-ALK, p-JNK, Nek7,and NLRP3 downstream molecules including activated caspase-1 (p20) and mature interleukin (IL)-1β (p17), were upregulatedin L. monocytogenes-infected macrophages. TheALK inhibitor significantly decreased the expression of p-JNK,Nek7, and NLRP3 downstream molecules in macrophages infectedwith L. monocytogenes. Furthermore, the Mst1/2 inhibitormarkedly inhibited the L. monocytogenes-induced activationof ALK, subsequently downregulating the expressionof p-JNK, Nek7, and NLRP3 downstream molecules. Therefore,our study demonstrated that Mst1/2-ALK mediatedthe activation of the NLRP3 inflammasome by promotingthe interaction between Nek7 and NLRP3 via JNK duringL. monocytogenes infection, which subsequently increased thematuration and release of proinflammatory cytokine to resistpathogen infection. Moreover, Listeriolysin O played akey role in the process. In addition, we also found that the L. monocytogenes-induced apoptosis of J774A.1 cells was reducedby the Mst1/2 or ALK inhibitor. The present study reported,for the first time, that the Mst1/2-ALK-JNK-NLRP3 signalingpathway plays a vital proinflammatory role during L. monocytogenesinfection.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Associations of TNF-RII rs1061622 With Post-Traumatic Stress Disorder and Their Interplays on Serum Lipids Levels in Adolescents

Ji Cheng Zhang,Jin Hua Wang,Jun Yi Liu,Qi Wei Guo,Jia Lin,Yi Lin Shen,Ke Xin Jia,Jia Jing Cai,Guo Ming Su,Ding Zhi Fang 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.11

Objective To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (<i>TNF-RII</i>) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents.Methods PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for <i>TNF-RII</i> rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods.Results G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD.Conclusion These results suggest reciprocal actions of <i>TNF-RII</i> rs1061622 with other factors on PTSD severity, interplays of <i>TNF-RII</i> rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of <i>TNF-RII</i> rs1061622 after experiencing traumatic events.