Objective: To investigate the effects of AZD5363, an inhibitor of protein kinase B (Akt), on proliferation, migration and apoptosis of human breast cancer cell line MDA-MB-231, and to further clarify their possible molecular mechanisms Methods: After treatment with different concentrations (0.5, 1, 5, 10, 20 and 50 μmol/L) of AZD5363, the viability of MDA-MB-231 cells was detected by MTT assay, the cell cycle distribution was analyzed by FCM, the cell migration ability was detected by wound healing test and Transwell chamber assay, the cell apoptosis rate was detected by TUNEL method. Then the expression levels of cell cycle- and apoptosis-related proteins were measured by Western blotting. Results: AZD5363 suppressed the cell viability in a dose-dependent manner (P < 0.05), and arrested the cell cycle progression at S phase by up-regulating the expression of p53 and down-regulating the expression of cyclin B1 (all P < 0.05). AZD5363 significantly inhibited the cell migration (P < 0.05), and induced the cell apoptosis (P < 0.05) by activating caspase-3 and poly (ADP-ribose) polymerase (PARP) proteins (both P < 0.05). Conclusion: AZD5363 can inhibit cell activity and migration, and induce apoptosis of human breast cancer cell line MDA-MB-2 31, thereby exhibiting its anticancer activity.

Objective To evaluate the diagnostic value of breast mass-like lesions by digital breast tomosynthesis technique (DBT) versus full field digital mammography (FFDM).Methods 182 breast mass cases undergoing respectively DBT and FFDM diagnosis were reviewed to evaluate the the sensitivity,specificity and accuracy,breast BI-RADS classification and differences of edge character.Results Of the 182 cases,101 cases were malignant,81 cases were benign.DBT and FFDM in malignant mass detection rate were 95.0％ and 95.0％ respectively,the benign tumor detection rate were 80.2％ and 80.2％ respectively,the difference was statistically significant (P ＜ 0.05).The diagnostic sensitivity was 93.1％ (94/101) and 82.2％ (83/101),specificity was 66.7％ (54/81) and 53.1％ (43/81),accuracy was 81.3％ (148/182) and 69.2％ (126/182),all the differences were statistically significant (P ＜ 0.05).The BI-RADS classification difference of the malignant mass was statistically significant (x2 =12.912,P =0.044 5),and the benign mass was also statistically significant (x2 =12.739,P =0.026 0).The clear edge benign tumors detected by DBT and FFDM respectively were 65 and 45 cases (x2 =10.224,P =0.001 4).The spicule sign detected by DBT and FFDM respectively in malignant tumors were 71 and 50 cases (x2 =8.244,P =0.004 1).Conclusion DBT compared to traditional FFDM photography improves the lesion visibility,increases the diagnostic sensitivity and specificity,conducing to the identification of benign and malignant lesions.

The axon guidance molecule Robo is a transmembrane protein which is conserved during evolution. Robo and its ligand, Slit, have been implicated in regulating many developmental processes, such as axon guidance, neuronal migration, tumor metastasis, angiogenesis, lung morphogenesis, kidney morphogenesis, heart morphogenesis, ovary development and gonad development. Robo function mainly depends on the binding of its Ig1 domain to the LRR-2 domain of Slit ligand. Meanwhile, Robo function is also mediated by binding to some signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs) and tyrosine kinase Abelson. Several transcription factors, including Hox, Midline and Nkx2.9, were shown to regulate robo expression. In addition, alternative splicing and transport regulation also affect Robo function. In this review, we summarized the studies on the molecular structure, functions and molecular mechanism of Robo, which would propose a novel strategy for the research of neural development, as well as prevention and treatment of nervous system diseases and cancers.
Axons ; physiology ; Nerve Tissue Proteins ; physiology ; Receptors, Immunologic ; physiology

Objective To investigate the action mechanism of long non-coding RNA(lncRNA)-N1LR on blood-brain barrier(BBB)after cerebral ischemia-reperfusion(I/R)injury.Methods Primary rat brain microvascular endothelial cells(BMECs)were cultured and treated with OGD/R to simulate cerebral I/R injury.The experiment was divided into normal control group,ln-cRNA-N1LR OGD group,overexpression group(lncRNA-N1LR overexpression after OGD treat-ment)and silence group(lncRNA-N1LR silence after OGD treatment).The mRNA levels of ln-cRNA-N1LR,claudin-5 and occludin in each group were detected by RT-qPCR.The BBB permea-bility was detected by FITC-dextran infiltration assay.The expression of claudin-5 and occludin were detected by Western blotting.Results The mRNA levels of lncRNA-N1LR,occludin and claudin-5 were significantly decreased(0.31±0.01 vs 1.00±0.10,0.42±0.03 vs 1.01±0.13,0.38±0.03 vs 1.00±0.15,P＜0.05),and the BBB permeability was significantly increased(58.79± 3.04 vs 8.87±0.63,P＜0.05)in the OGD group than the control group.The lncRNA-N1LR over-expression group increased the mRNA expression of lncRNA-N1LR,occludin and claudin-5(0.67±0.07 vs 0.31±0.01,0.92±0.02 vs 0.42±0.03,0.70±0.08 vs 0.38±0.03,P＜0.05),and decreased the BBB permeability(41.57±2.43 vs 58.79±3.04,P＜0.05)than the OGD group.lncRNA-N1LR silence resulted in lower mRNA levels of lncRNA-N1LR,occludin and claudin-5(0.21±0.02 vs 0.31±0.01,0.31±0.03 vs 0.42±0.03,0.22±0.02 vs 0.38±0.03,P＜0.05),and enhanced BBB permeability(72.34±1.43 vs 58.79±3.04,P＜0.05)when compared with the OGD group.Conclusion Up-regulation of lncRNA-N1LR may play a neuroprotective role by reducing BBB permeability.

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins