The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.

Objective The aims of this study were to investigate the expression of DKK2,a WNT signaling pathway regula-tor,in nephroblastoma cells and tissues of children,the effect on the proliferation of nephroblastoma SK-NEP-1 cells,and to explore its mechanism. Methods The relative expression of DKK2 in nephroblastoma cells and tissues was analyzed by qRT-PCR and im-munoblotting assays. Overexpressing DKK2 SK-NEP-1 cells were set as the experimental group( DKK2 group);the blank control plasmid group was set as a control group( Vector group),transfected with pcDNA3. 1 ( +) -Flag-DKK2 plasmid( Experimental group)and pcDNA3. 1( +) -Flag-Vector plasmid(Control group). The over-expression of DKK2 was confirmed in SK-NEP-1 cells by RT-PCR and immunoblotting. CCK-8 and cell cloning assays were used to determine the effect of DKK2 on cell prolifera-tion;flow cell cycle and apoptosis assays were used to confirm the effect on cell proliferation in overexpressed DKK2 cells. The xen-graft formation assay in nude mice was to verify the effect of DKK2 on proliferation in overexpressed DKK2 cells;the mechanism of DKK2 in inhibitory proliferation was analyzed by qRT-PCR,Western blotting and immunohistochemistry. Results Compared with normal renal epithelial tissues,DKK2 mRNA was down-regulated in children with nephroblastoma,and the difference was statistically significant(P<0. 001). Compared with the control group,transfected DKK2 cell viability was significantly inhibited after treatment for 24,48 and 72 h( P<0. 05),cell clone formation in the experimental group was significantly inhibited(31. 11% ± 2. 14% ) ( P<0. 05),the cell cycle in the experimental group was significantly arrested at the G1 phase(P<0. 001),and the apoptosis rate in the experimental group was significantly increased(P<0. 001). Compared with the control group,the tumor weight and volume in nude mice were significantly low in the experimental mice which were injected DKK2 overexpression cells(P<0. 001). Active-β-cate-nin and downstream genes were significantly inhibited in over-expressed DKK2 SK-NEP-1 cells. Conclusion DKK2 is down-regulated in human cutaneous nephroblastoma and participates in the mechanism of nephroblastoma by antagonizing Wnt/β-catenin signaling pathway.

Objective:Healthy life expectancy (HLE), which combines life expectancy with health, is an essential comprehensive measure of life length and quality. This article aimed to systematically review the methods for defining and measuring HLE and describe application studies published, providing a reference for decision makers to select and develop methods suitable for China's conditions to measure HLE.Methods:Seven Chinese and English literature databases were searched up to May 7, 2022, and several related reviews and bibliography were manually retrieved. Systematic reviews and empirical research were included concerning HLE indicators and measurement of HLE. Information including the study area, type of the study, study population, HLE index, measurement method, data sources, and results from application studies published in the last five years were extracted. The evolution of the definition of HLE, the scope of different indicators, the measurement scale of health, and measurement methods, were all collected. Results of the empirical research related to measurement methods of indicators were summarized. The study followed the scoping review framework and was written according to the PRISMA-ScR statement.Results:A total of 84 articles were included, including 13 reviews, 17 original studies related to HLE index definition, ten original studies related to index measurement, and 44 empirical studies conducted in the past five years. There were as many as 20 indicators related to HLE, and each scale had its emphasis. A total of ten methods measuring HLE were identified, which vary in the definition of health, whether using weight, and the data type. The most commonly used indicators in the past five years were disability-free life expectancy and HLE. For the method of HLE calculation, Sullivan's method was mainly used for cross-sectional data, and the multistate life table was mainly used for longitudinal data.Conclusions:There are various definitions and measurement methods of HLE, but none are suitable for all scenarios. To summarize the HLE concept, health evaluation techniques, measurement methods, and application studies published worldwide can provide a reference for the localization of HLE measurement in China.

Objective To explore the effect of mucle force on contact force, peak pressure and contact area of foot joint in in vitro biomechanical experiment of foot and ankle, so as to provide references for choosing appropriate loading modes. Methods In neutral position of the ankle joint, fresh calf and foot specimens were simulated with or without mucle force loading. The contact force, peak pressure and contact area of the 1st metatarsophalangeal joint, the 2nd metatarsophalangeal joint, the 1st tarsometatarsal joint, the 2nd tarsometatarsal joint, the medial cuneonavicular joint, the intermediate cuneonavicular joint, the talonavicular joint, the calcicocuboid joint, the subtalar joint ( posterior articular surface) and the tibiotalar joint of normal foot under loading were measured, the results are compared and analyzed. Results Under muscle force loading, the contact force of the 1st metatarsophalangeal joint, the 2nd metatarsophalangeal joint, the 1st tarsometatarsal joint,the 2nd tarsometatarsal joint, the medial cuneonavicular joint, the intermediate cuneonavicular joint, the talonavicular joint and the tibiotalar joint were significantly greater than those without muscle force loading (P<0. 05), and the change percentages were 719. 28% , 311. 37% , 128. 67% , 50. 82% , 54. 89% , 57. 63% ,79. 98% and 50. 34% , respectively. The peak pressures of the 1st metatarsophalangeal joint , the 1st tarsometatarsal joint and the talonavicular joint under muscle force loading were significantly higher than those without muscle force loading ( P < 0. 05), and the change percentages were 176. 14% , 62. 91% and 40. 07% ,respectively. The contact area of the 1st metatarsophalangeal joint, the 1st tarsometatarsal joint, the intermediate cuneonavicular joint and the subtalar joint ( posterior articular surface) under muscle force loading increased significantly (P<0. 05), and the change percentages were 132. 20% , 55. 41% , 30. 97% and 26. 87% , respectively. Conclusions In biomechanical experiment of foot and ankle specimens, muscle force loading has a significant effect on contact force, peak pressure and contact area of each foot joint, especially the forefoot.Therefore, it is necessary to consider the effect of muscle force loading on stress of foot and ankle in the study ofrelated in vitro specimens