Discovery of the anti-angiogenesis effect of eltrombopag in breast cancer through targeting of HuR protein

HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited cell proliferation of multiple cancer cell lines and macrophages, and the anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.

Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood-brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.

Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

Effects of ginkgo biloba extract on CRP and TNF-α in rats with chronic obstructive pulmonary disease / 实用医学杂志

Objective To study the effects of ginkgo biloba extract(GBE)on c-reactive protein(CRP) and tumor necrosis factor-α(TNF-α)in serum and alveolar lavage fluid(BALF)from rats with chronic obstructive pulmonary disease(COPD). Methods 90 rats were randomly divided into groups A,B,C,D,E and F. There were 15 rats in each group. The rat model of COPD were established in groups B,C,D,E and F. Groups C and D were given intraperitoneal injections with GBE from day l to day l4 and day 29 to day 42. Groups E and F weregiven intraperitoneal injections with erythromycin from day l to day l4 and day 29 to day 42. After the end of experi-ment ,the contents of CRP and TNF-α in serum and BALF were detected in all groups. Results The contents of CRP and TNF-α in the serum and the BALF were markedly lower in groups C,D,E and F than in group B (P<0.05);and the contents of CRP in the serum and the BALF and TNF-αin the BALF were lower in groups C, E and F than in group D(P<0.05). Conclusions GBE can inhibit the airway and systemic inflammatory response in COPD rats. Early intervention is more effective.

A cross-sectional survey on the patterns of primary teeth eruption in 2 581 children / 中华儿科杂志

Objective@#To investigate the patterns of primary teeth eruption by a cross-sectional survey in 0-40 months old children in Chongqing and to provide normal timetables of tooth eruption that are practical in general physical growth assessment.@*Method@#Data of 2 581 0-40 months old healthy children were collected from January 2014 to January 2016 at Children′s Hospital of Chongqing Medical University. General information was recorded by primary child health care doctors, including age, gender, gestation age, birth weight, time and sequence of first primary tooth eruption, number of teeth and age of totally primary teeth emergence. Median and constituent ratio were used in describing the age of tooth eruption and eruption characteristics at different age. Moreover, independent-sample t test, variance analysis, Pearson product-moment correlation and Logistic regression were also involved in data analysis.@*Result@#Totally 2 581 children were involved in this survey, including 506 infants of 0-6 months old, 600 infants of 7-12 months old, 730 toddlers of 13-24 months old and 745 children of 25-40 months old. There were 1 473 boys and 1 108 girls, 89 preterm babies and 2 492 full term babies, 1 829 children with tooth erupted and 626 children with all primary teeth erupted.The age of the first primary tooth eruption was between 2-15 months old ( median age: 8 months old, 95%CI: 2.7-12.7)and for the last primary tooth emergence was between 23-35 months of age (median age: 31 months, 95%CI: 24.7-36.7). The time of first tooth eruption was positively correlated with that of total teeth emergence (r=0.879, P<0.05). Dental charts (number of tooth for age) of different gender were drawn according to teeth eruption information. The first primary tooth eruption was the incisor of mandible in 95.3% (1 743/1 829)infants and was the incisor of maxilla in 4.6% (84/1 829)infants. During the period of tooth emerging actively (number of teeth ≤16), the number of primary teeth might be calculated by formula: number of teeth=chronological age in months-age of first eruption in months+ 1. There was no statistically significant difference between the number of actual teeth and calculated by the present formula(t=-2.957, P=0.05).@*Conclusion@#The median age of first primary tooth eruption and total teeth emergence was 8 and 31 months of age respectively. The first primary tooth eruption is incisor of mandible in most infants.The formula (number of teeth=chronological age in months-age of first eruption in months+ 1 )can be used to estimate the number of primary teeth. Dental charts might provide normal and supplement datasets for evaluating child physical growth.

Effect of pathophysiology case-based learning(CBL)method on scores of pediatrics / 中华医学教育探索杂志

Objective To investigate the effect of pathophysiology case-based learning(CBL)method on scores of pediatrics.Methods Undergraduates from 2005 grade at Chengde medical college were divided into two groups:experimental group(n=138,CBL method)and control group(n=136,conventional teaching method).The scores of pediatrics between the two groups were compared.The pediatrics test paper was divided into two types:type B,which was tightly connected with the pathophysiology knowledge and type F,which had less connection with pathophysiology knowledge.The accuracy rates of both groups were compared.Correlation analysis on scores between pathophysiology and internal medicine,surgery,pediatrics,obstetircs and gynaecology was made.Results No significant difference in total scores of pediatrics was observed between the two groups(P＞0.05);total accuracy rate of experimental group was higher than that of control group(P＞0.05);similar total accuracy rates of type F test paper were observed in both groups(P＞0.05);positive correlations in scores between pathophysiology and internal medicine,surgery,pediatrics,obstetircs and gynaecology were found.Conclusions Satisfactory long-term effect are received by applying pathophysiological CBL model since it can promote the application of pathophysiological knowledge in pediatrics,however,no apparent effect on students'clinical ability can be obtained from the mere application of CBL in pathophysiology course.

Relationships of human laryngeal squamous cell carcinomas with the expression of VEGF-C and VEGFR-3 / 生物医学工程学杂志

In order to detect the relationships of human laryngeal squamous cell carcinoma (LSCC) with the expression of Vascular Endothelial Growth Factor C (VEGF-C) and Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3), we examined the level of VEGF-C and VEGFR-3 gene expression in the samples from 30 cases of normal laryngeal mucosa tissue (NLM), primary laryngeal carcinoma (PLC) and cervical lymph node (CLN) by using reverse transcription polymerase chain reaction (RT-PCR). The protein levels of VEGF-C and VEGFR-3 expression were also determined by Western blotting in 10 cases of NLM, PLC, CLN,respectively. We found that in the samples from the same patient, the VEGF-C and VEGFR-3 expression level is different among normal laryngeal mucosa tissue, primary laryngeal carcinoma and cervical lymph node. In primary laryngeal carcinoma, the level of VEGF-C and VEGFR-3 expression was significantly higher in lymph node positive group than in lymph node negative group, and this difference was the associated with the histological grade of differentiation (P < 0.05). The expression levels of VEGF-C and VEGFR-3 were not associated with age, sex, site and T stage (P > 0.5). These results suggest that there is a close relationship of LSCC with VEGF-C/VEGFR-3; and VEGF-C/VEGFR-3 may have the potential for use as an indicator with prognostic significance in dealing with LSCC.

Expression of CEA,ICAM-1 on lymphatic endothelial cells in rectum cancer of human / 中国现代普通外科进展

Objeetive:To study the expression of cell adhesion molecules on the lymphatic endothelial cells In the rectum cancer and peritumoral lymph nodes as well as their relationship with the diffusion of cancer cellS. Methods: In this Study the immunhistochemistry method was employed to observe the expression of CEA, ICAM-1 and CD31 on rectum cancer lymphatic endo-thelial cells. Results :The results demonstrated that CEA and lCAM-1 were highly expressed on the lynphatio endothelial cells in the peritumoral rectum tissues and lymph nodes. It was, howev-er,negative in normal lymphatic endothelial cells. CD31 was expressed on both lymphatic endothe-Ilal cells in the periturmral rectum tissues and lymph nodes and vessel endothelial cells of the normal human. Conelusion: The study suggests that there are relationships between the dis-semination of cancer cells and excession of CEA, lCAM-1 and CD31 in lymphatic endothelial cells.The CAE and ICAM-1 seem to induce stable adhesion between oancer cells and endothelial cells.

Immunohistochemical Study of Insulin-Like Growth Factor-I in Human Fetal Organs / 解剖科学进展

Objective　To study the distribution of insulin-like Growth Factors (IGFs) in liver、 spleen、kidney、thymus and supraadrenal glands of fetus from 16 to 24 weeks.Method　Using ABC immunohistochemistry. Results　 IGF-I positive cells were found in these organs during this period of fetal life, but the differences of number and reaction intensity of IGF-I positive cells appeared in different organs and individuals.Conclusion　These organs tissues can express IGF-I during fetal development and play paracrine and/or autocrine role in cellular proliferation and differentiation of these fetal tissue.

The distributive characteristics of glial cell line-derived neurotrophic factor in brain tissue during ischemia-reperfusion in rats / 临床神经病学杂志

Objective To observe the distributive characteristics of glial cell line-derived neurotrophic factor(GDNF)in brain tissue during cerebral ischemia-reperfusion in rats,and its role in ischemic brain damage.Methods The model of focal cerebral ischemia was made by occluding middle cerebral artery(MCA) for 2 h and reperfusion for 0.5～48 h, HE Staining was used to investigate the histological features of ischemic cerebral damage,the immunohistochemical method was used to observe the distributive characteristics of GDNF in brain tissue in rats. Results The focal ischemic areas (including preoptic area, striatum and cortex) presented at 0.5 h of reperfusion and peaked at 24 h. The neurons presented irreversible degeneration at 6 h of reperfusion. At 24 h, the ischemic area in the preoptic area developed into infarct form. At 0.5 h of reperfusion, neurons in ischemic cortex showed GDNF weak positive, neurons in peri-ischemic regions showed GDNF moderate positive. During reperfusion 3～48 h, neurons in ischemic regions showed GDNF negative. Up to 48 h of reperfusion, the active microglias or macroglias in periinfart area strongly expressed GDNF.The number of GDNF positive cells in all groups decreased (P

The Applied Value of Selected Intraoperative Cholangiography in Cholecystectomy / 实用放射学杂志

Objective To evaluate the applied of selected intraoperative cholangiography(SIOCG) during cholecystectomy.Methods The SIOCG data of 39 patients who had indications for exploration of common bile duct were analysed retrospectively.Results Among 39 cases with SIOCG,abnormal findings were detected in 19 cases(48.72%),in which choledocholith in 16 cases;stenosis of common bile duct at the third part in 3 cases.Positive findings in exploration of common bile duct were 14 cases(73.68%),in which,choledocholith were 12 cases inflammatory stenosis 1 case and tumor of common bile duct at the third part 1 case.Negative patients in exploration of common bile duct were 5 cases(26.32%).Normal imaging in 20 patients who did not underwent exploration of common bile duct had no disorders in follow-up.Conclusion SIOCG is safe,convenient,and useful in preventing the remnant stones and biliary tract damage and improving the quality of cholecystectomy.