Effective Antiviral Activity of the Tyrosine Kinase Inhibitor Sunitinib Malate against Zika Virus

Background@#(Introduction): Zika virus (ZIKV), a mosquito-borne flavivirus, causes the outbreaks of Latin America in 2015 - 2016, with the incidence of neurological complications. Sunitinib malate, an orally bioavailable malate salt of the tyrosine kinase inhibitor, is suggested as a broadspectrum antiviral agent against emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. @*Materials and Methods@#This study investigated the antiviral efficacy and antiviral mechanisms of sunitinib malate against ZIKV infection using cytopathic effect reduction, virus yield, and time-of-addition assays. @*Results@#Sunitinib malate concentration-dependently reduced ZIKV-induced cytopathic effect, the expression of viral proteins, and ZIKV yield in supernatant with 50% inhibitory concentration (IC 50 ) value of 0.015 μM, and the selectivity index of greater than 100 against ZIKV infection, respectively. Sunitinib malate had multiple antiviral actions during entry and post-entry stages of ZIKV replication. Sunitinib malate treatment at entry stage significantly reduced the levels of ZIKV RNA replication with the reduction of (+) RNA to (-) RNA ratio and the production of new intracellular infectious particles in infected cells. The treatment at post-entry stage caused a concentration-dependent increase in the levels of ZIKV (+) RNA and (-) RNA in infected cells, along with enlarging the ratio of (+) RNA to (-) RNA, but caused a pointed increase in the titer of intracellular infectious particles by 0.01 and 0.1 μM, and a substantial decrease in the titer of intracellular infectious particles by 1 μM. @*Conclusion@#The study discovered the antiviral actions of sunitinib malate against ZIKV infection, demonstrating a repurposed, host-targeted approach to identify potential antiviral drugs for treating emerging and global viral diseases.

Cis-3-O-p-hydroxycinnamoyl Ursolic Acid Induced ROS-Dependent p53-Mediated Mitochondrial Apoptosis in Oral Cancer Cells

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 µM and 17.8 µM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.

Clinical experience of orthodontic treatment on 36 cases with congenital lower incisor missing / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To explore the treatment plan in patients with congenital lower incisor missing.</p><p><b>METHODS</b>Thirty-six patients with congenital lower incisor missing were included in the investigation. The missing location, missing quantity, malocclusion type and treatment method were analyzed. Bolton index of two groups were analyzed. The first group was congenital missing one lower incisor who treated by extracting two upper first premolars and one lower first premolar. The second group was congenital missing two lower incisors who treated by exacting two upper first premolars.</p><p><b>RESULTS</b>The therapeutic effect of 36 cases were better. Overall ratio in two groups were 91.70% +/- 1.85% and 92.83% +/- 2.74%, anterior ratio were 81.69% +/- 2.12% and 85.46% +/- 2.39%, anterior tooth-size discrepancy were (2.16 +/- 0.64) mm and (4.27 +/- 1.14) mm. There were no significance difference on overall ratio in two groups (P > 0.05). There were significance difference in anterior ratio and anterior tooth-size discrepancy (P < 0.01).</p><p><b>CONCLUSION</b>For patients with congenital missing one lower incisor who need extraction in upper and lower jaws, it is less affection on Bolton index that extracting one premolar at non-missing side than extracting one center incisor in mandible.</p>

Clinic study of root resorption caused by edgewise appliance combined with flat bite plate treatment / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the root resorption caused by edgewise appliance combined with flat bite plate treatment.</p><p><b>METHODS</b>65 patients with edgewise technique and flat bite plate treatment were chosen. All patients were taken panoramic radiograph before flat bite plate treatment, immediately after flat bite plate treatment and 6 months after flat bite plate treatment. Root resorption grade of mandibular permanent incisors were analyzed.</p><p><b>RESULTS</b>There were statistical difference in the root resorption grade of three groups (P < 0.05), but there was no statistical difference between male and female (P > 0.05).</p><p><b>CONCLUSION</b>Flat bite plate can cause root resorption of mandibular permanent incisors, but the root resorption is slight.</p>