Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC₅₀) was 13.8 μmol·L^-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC₅₀: 41.99 μmol·L^-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

AlM: To observe the effect of anterior chamber depth and angle change after pterygium excision.METHODS:Thirty cases (30 eyes) of primary pterygium were underwent pterygium excision. Central anterior chamber depth, four direction angle open distance ( AOD ) and open angle ( AA ) were measured preoperatively and postoperatively by ultrasound biomicroscopy ( UBM ) and the intraocular pressure was observed.RESULTS:Preoperative and Postoperative intraocular pressure were 15. 17±10. 6 and 16. 23±2. 61mmHg, and the central anterior chamber depth were 2. 28±0. 39 and 2. 33± 0. 24mm. The four directions of AOD and AA were no statistical difference.CONCLUSlON:The anterior chamber depth and the angle change is not obvious after pterygium excision.

OBJECTIVE: Over-expression of thrombin in ovarian cancer cells is associated with poor prognosis. In this study, we investigated the role of thrombin in inducing epithelial-mesenchymal transition (EMT) in SKOV3 epithelial ovarian cancer cells. METHODS: After thrombin treatment SKOV3 cells were subjected to western blots, reverse-transcription PCR, and enzyme-linked immunosorbent assay to quantify EMT-related proteins, mRNA expression of SMAD2, DKK1, and sFRP1, and the secretion of matrix metalloproteinases (MMPs) and cytokines. Meanwhile, invasion ability was evaluated using transwell assays. RESULTS: The results indicated a dose- and time-dependent down-regulation of E-cadherin and upregulation of N-cadherin and vimentin in thrombin-treated SKOV3 cells, compared with the thrombin-free control group (p<0.05). There was a dose- and time-dependent increase in the levels of SMAD2 and DKK1 mRNAs and a decrease in the levels of sFRP1 mRNA in thrombin-treated SKOV3 cells compared to control cells (p<0.05). Thrombin-treated SKOV3 cells exhibited increased secretion of MMP-9, MMP-2, interleukin (IL)-8, and IL-6 and increased invasion compared to untreated cells (p<0.05). Thrombin altered the morphology of SKOV3 cells to a spindle-like phenotype. Addition of hirudin to thrombin-treated cells reversed the effects of thrombin. CONCLUSION: Thrombin induced EMT and promoted the invasion of SKOV3 cells, possibly via distinct signaling pathways. Hirudin inhibited the effects of thrombin, suggesting that anticoagulant therapy could be a novel therapeutic strategy for ovarian carcinoma.
Blotting, Western ; Cadherins ; Cytokines ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Epithelial-Mesenchymal Transition ; Hirudins ; Interleukin-6 ; Interleukins ; Matrix Metalloproteinases ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Phenotype ; Polymerase Chain Reaction ; Prognosis ; Proteins ; RNA, Messenger ; Thrombin ; Up-Regulation ; Vimentin

Retinoblastoma (RB) is one of the most common primary intraocular malignant tumors of children. With improvement of the medical care, the goal of RB treatment is saving the eyeball and even the vision. In the process of globe-salvaging treatment, complicated cataract has been a serious problem which affects the treatment and follow-up. It is important to operate a cataract surgery timely and safely. In this paper related research advances were summarized.

measured by OCT 1 and 3mo after surgery. Chi-square test was used to compare preoperative and postoperative BCVA. Pearsion’s correlation was used to evaluate relationship between postoperative BCVA and central foveal thickness.RESULTS:The ratio of BCVA<0. 05 was 30%,14%, 11%and 7% respectively for per-operation, 1wk, 1 and 3mo post - operation. After surgery, the central foveal thickness was significantly increased in group with BCVA<0. 3 comparing to group with BCVA≥0. 3. Three month post-operation, central foveal thickness was significantly decreased in both groups comparing to that in 1mo post-operation (P<0. 01). There has significant correlation between 3mo postoperative BCVA and central foveal thickness (r=-0.716, P<0.05).CONCLUSlON: ln this study, BCVA is improved after 3mo follow up. There has significant correlation between postoperative BCVA and central foveal thickness.

OBJECTIVEThis report aims to describe the oxidative damage profile in brain of presenilin1 and presenilin2 conditional double knockout mice (dKO) at both early and late age stages, and to discuss the correlation between oxidative stress and the Alzheimer-like phenotypes of dKO mice.

METHODSThe protein level of Abeta(42) in dKO cortex and free 8-OHdG level in urine were measured by ELISA. Thiobarbituric acid method and spectrophotometric DNPH assay were used to determine the lipid peroxidation and protein oxidation in cortex, respectively. SOD and GSH-PX activities were assessed by SOD Assay Kit-WST and GSH-PX assay kit, separately.

RESULTSSignificant decrease of Abeta(42) was verified in dKO cortex at 6 months as compared to control mice. Although lipid peroxidation (assessed by MDA) was increased only in dKO cortex at 3 months and protein oxidation (assessed by carbonyl groups) was basically unchanged in dKO cortex, ELISA analysis revealed that free 8-OHdG, which was an indicator of DNA lesion, was significantly decreased in urine of dKO mice from 3 months to 12 months. Activities of SOD and GSH-PX in dKO and control cortices showed no statistical difference except a significant increase of GSH-PX activity in dKO mice at 9 months.

CONCLUSIONOxidative damage, especially DNA lesion, was correlated with the neurodegenerative symptoms that appeared in dKO mice without the deposition of Abeta(42). Triggers of oxidative damage could be the inflammatory mediators released by activated microglia and astrocytes.

Age Factors ; Alzheimer Disease ; genetics ; metabolism ; physiopathology ; Amyloid beta-Peptides ; urine ; Animals ; Deoxyguanosine ; analogs & derivatives ; urine ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; methods ; Glutathione ; metabolism ; Hydrazines ; metabolism ; Lipid Peroxidation ; genetics ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred CBA ; Mice, Knockout ; physiology ; Oxidation-Reduction ; Oxidative Stress ; physiology ; Peptide Fragments ; urine ; Presenilin-1 ; deficiency ; Presenilin-2 ; deficiency ; Spectrophotometry, Atomic ; methods ; Superoxide Dismutase ; metabolism

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.