MiR-140 targets Wnt1 to inhibit the proliferation and enhance drug sensitivity in osteosarcoma cells.

MicroRNAs (miRNAs) have been documented to function differently in numerous human cancers. Our study planned to investigate the role of microRNA-140 (miR-140) and to identify its possible target in osteosarcoma (OS) to predict their mechanism in OS. The miR-140 was down-regulated in OS, and its high expression decreased MG63 cell proliferation. At the molecular level, Wnt1 was a target of miR-140, and its expression could be suppressed by miR-140. Besides, miR-140 overexpression decreased drug resistance in OS cells treated by doxorubicin. Collectively, overexpression of miR-140 may inhibit human OS cell proliferation and may enhance drug sensitivity by direct regulation of Wnt/ß-catenin signaling.

Effect of N-cadherin on Chondrogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells through Wnt Signaling Pathway.

This study aimed to compare and analyze the effect of N-cadherin on chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and to explore the related mechanism, so as to provide a novel theoretical basis for the clinical work of articular cartilage injury regeneration and repair. For this purpose, the experimental animals were clean grade SD rats (aged 5-6 weeks, weighing 180-250g). Alcian blue staining was carried out to observe the induced chondrogenesis following N-cadherin inhibition. The specific role of N-cadherin in the Wnt signaling pathway and chondrogenic differentiation of BMSCs was detected by Western blot; while the effect of N-cadherin on the molecular level changes of ß-catenin in the cytoplasm was evaluated by fluorescence quantitative real-time PCR (qRT-PCR). In addition, immunoprecipitation (IP) was used for the verification of the interaction between N-cadherin and ß-catenin. Results showed that under the light microscope, 90% of the BMSCs at the third generation, 90% of the cells were fused. Alcian blue staining showed that the green staining area in the BMP2 induction group was large and dense, while that in the N-cadherin inhibition group and blank control group was small and sparse. Western blot revealed that N-cadherin and SOX9 were significantly developed in the BMP2 induction group, but Wnt3a was not significantly developed. While in the N-cadherin inhibition group, the development of Wnt3a was obvious, yet without evident development of N-cadherin and SOX9. The qRT-PCR indicated that the relative mRNA expression of Wnt3a was significantly increased in the N-cadherin inhibition group (P<0.05). However, no obvious difference was observed in the mRNA expression of ß-catenin between the BMP2 induction group and the N-cadherin inhibition group (P>0.05). Western blot indicated that in the BMP2 induction group; there existed the development of ß-catenin, significant development of phos-GSK-3ß and total GSK-3ß, but no obvious development of Wnt3a. In the N-cadherin inhibition group, there was significantly enhanced development of Wnt3a and ß-catenin than that before, blurred development of phos-GSK-3ß than that before, and also obvious development of total GSK-3ß with little change from before. N-cadherin promoted the expression of ß-catenin mostly in the cell membrane, but only a few in the cytoplasm and nucleus. Additionally, verification by IP showed that N-cadherin and ß-catenin were developed on N-cadherin and ß-catenin bands, suggesting an interaction between N-cadherin and ß-catenin. According to these results, N-cadherin can ultimately promote chondrogenic differentiation of BMSCs by inhibiting the Wnt signaling pathway.

Save lives or save livelihoods? A cross-country analysis of COVID-19 pandemic and economic growth.

This paper studies whether containing COVID-19 pandemic by stringent strategies deteriorates or saves economic growth. Since there are country-specific factors that could affect both economic growth and deaths due to COVID-19, we first start with a cross-country analysis on identifying risk and protective factors on the COVID-19 deaths using large across-country variation. Using data on 100 countries from 3 January to 27 November 2020 and taking into account the possibility of underreporting, we find that for deaths per million population, GDP per capita, population density, and income inequality are the three most important risk factors; government effectiveness, temperature, and hospital beds are the three most important protective factors. Second, inspired by the stochastic frontier literature, we construct a measure of pandemic containment effectiveness (PCE) after controlling for country-specific factors and rank countries by their PCE scores for deaths. Finally, by linking the PCE score with GDP growth data in Quarters 2 and 3 of 2020, we find that PCE is positively associated with economic growth in major economies. Countries with average PCE scores, such as Malaysia, would gain more GDP growth by 3.47 percentage points if they could improve their PCE scores for deaths to South Korea's level in Q2 of 2020. Therefore, there is not a trade-off between lives and livelihood facing by governments. Instead, to save economy, it is important to contain the pandemic first. Our conclusion is also mainly valid for infections due to COVID-19.

Sunitinib as first-line neoadjuvant therapy in two patients with rectal stromal tumors.

In the treatment of rectal stromal tumors, which account for approximately 5% of gastrointestinal stromal tumors, molecular-targeted neoadjuvant therapy should be considered if the tumor is too large to achieve R0 grade resection or multiple visceral resection is required. Currently, imatinib is generally recommended as the first-line agent for such therapy. Although it has been reported that neoadjuvant therapy in patients experiencing imatinib resistance or intolerable adverse events can be successfully achieved by switching to sunitinib, first-line use of sunitinib for neoadjuvant therapy of gastrointestinal stromal tumors has not previously been reported. In this case report, first-line sunitinib neoadjuvant therapy of two patients who had very large rectal stromal tumors at sites close to the prostate and bladder produced good clinical outcomes.