No abstract

Background: Crosstalk between cancer cells and tumor-associated macrophages (TAMs) mediates tumor progression in colorectal cancer (CRC). Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been shown to exhibit tumor-suppressive role in CRC. Methods: The expression of CPEB3, CD68, CD86 and CD163 was determined in CRC tissues. SW480 or HCT116 cells overexpressing CPEB3 and LoVo or RKO cells with CPEB3 knockdown were constructed. Stably transfected CRC cells were co-cultured with THP-1 macrophages to determine the malignant phenotype of CRC cells, macrophage polarization, and secretory signals. The inhibition of CPEB3 on tumor progression and M2-like TAM polarization was confirmed in nude mice. Results: Decreased CPEB3 expression in CRC was associated with fewer CD86+ TAMs and more CD163+ TAMs. CPEB3 knockdown in CRC cells increased the number of CD163+ TAMs and the expression of IL1RA, IL-6, IL-4 and IL-10 in TAM supernatants. TAMs enhanced CRC cell proliferation and invasion via IL-6, and then activated the IL-6R/STAT3 pathway in CRC cells. However, CPEB3 reduced the IL-6R protein levels by directly binding to IL-6R mRNA, leading to decreased phosphorylated-STAT3 expression in CRC cells. CCL2 was significantly increased in CPEB3 knockdown cells, while CCL2 antibody treatment rescued the effect of CPEB3 knockdown in promoting CD163+ TAM polarization. Eventually, we confirmed that CPEB3 inhibits tumor progression and M2-like TAM polarization in vivo. Conclusions: CPEB3 is involved in the crosstalk between CRC cells and TAMs by targeting IL-6R/STAT3 signaling.

By matching air quality index (AQI) data with the household data from China Family Panel Studies (CFPS), we identify the impact of air pollution on household medical expenses from a micro perspective. The results show that higher air pollution will increase household medical expenses and change household consumption structure. This effect is still significant after controlling for cities' relevant household and individual characteristics and economic characteristics. Under different educational backgrounds, income, hukou, gender, and other conditions, air pollution will significantly reduce medical spending. For those females in the urban areas with higher education backgrounds and higher income, the spending elasticity of air pollution is more significant than other corresponding groups. And air pollution will promote medical expenses through stronger individuals' environmental awareness, poor health conditions, bad emotional status, and positive risk aversion. Furthermore, we find that the impact of air pollution on healthcare spending remains significant after instrumental variables regression and geographical regression based on the Qinling Mountains-Huaihe River Line.

Background: Crosstalk between cancer cells and tumor-associated macrophages (TAMs) mediates tumor progression in colorectal cancer (CRC). Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been proved to exhibit tumor suppressive role in CRC.Methods: The expression of CPEB3, CD86 and CD163 was determined in CRC tissues. SW480 or HCT116 cells with overexpressed CPEB3 and LoVo or RKO cells with knockdown CPEB3 were constructed. Stably transfected CRC cells were co-cultured with THP-1 macrophages to determine the malignant phenotype of CRC cells, the macrophage polarization and the secretory signals. The inhibition of CPEB3 on tumor progression and M2-like TAM polarization was confirmed in nude mice.Results: Decreased CPEB3 expression in CRC was associated with less CD86+ TAMs number and more CD163+ TAMs number. CPEB3 knockdown in CRC cells increased CD163+ TAMs number and the expression of IL1RA, IL-6, IL-4 and IL-10 in TAMs supernatants. TAMs enhanced CRC cells proliferation and invasion via IL-6, then activated the IL-6R/STAT3 pathway in CRC cells. However, CPEB3 reduced the IL-6R protein level by directly binding to IL-6R mRNA, leading to decreased phosphorylated-STAT3 expression in CRC cells. CCL2 was significantly increased in knockdown CPEB3 cells, while CCL2 antibody treatment rescued the effect of knockdown CPEB3 on promoting CD163+ TAMs polarization. Eventually, we confirmed that CPEB3 inhibits tumor progression and M2-like TAMs polarization in vivo. Conclusions: CPEB3 is involved in the crosstalk between CRC cells and TAMs by targeting IL-6R/STAT3 signaling.