Xiaoying Xu

Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

LncRNA TUG1, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, its biological function in thyroid cancer cells has not been elucidated. The aim of this study is to measure TUG1 expression level and evaluate its function in thyroid cancer cells. LncRNA TUG1 expression levels in thyroid cancer tissues and three thyroid cancer cell lines (the ATC cell lines SW1736 and KAT18 and the FTC cell line FTC133) were assessed by qRT-PCR and compared with that of the human normal breast epithelial cell HGC-27. MTT assay, colony formation assay, transwell assay and western blot analysis were performed to assess the effects of TUG1 on proliferation, metastasis and EMT formation in thyroid cancer cells in vitro. Rescue assay was performed to further confirm that TUG1 contributes to the progression of thyroid cancer cells through regulating miR-145/ZEB1 signal pathway. LncRNA TUG1 was found to be up-regulated in thyroid cancer tissues and thyroid cancer cells compared with that in the human normal breast epithelial cell HGC-27. Increased lncRNA TUG1 expression was found to significantly promote tumor cell proliferation, and facilitate cell invasion, while down-regulated TUG1 could obviously inhibit cell proliferation, migration/invasion and reverse EMT to MET. These results indicated that TUG1 may contribute to the progression of thyroid cancer cells by function as a ceRNA competitive sponging miR-145, and that lncRNA TUG1 is associated with tumor progression in thyroid cancer cells.

BACKGROUND: To evaluate the independent and joint effects of maternal pre-pregnancy BMI and gestational weight gain (GWG) on the risk of preeclampsia and its subtypes. METHODS: A birth cohort study was conducted from 2010 to 2012 in Lanzhou, China. Three hundred fourty seven pregnant women with preeclampsia and 9516 normotensive women at Gansu Provincial Maternity and Child Care Hospital were included in the present study. Unconditional logistic regression models were used to evaluate the associations between pre-pregnancy BMI, GWG, and risk of preeclampsia and its subtypes. RESULTS: Compared to women with normal pre-pregnancy BMI, those who were overweight/obese had an increased risk of preeclampsia (OR = 1.81; 95%CI: 1.37-2.39). Women with excessive GWG had an increased risk of preeclampsia (OR = 2.28; 95%CI: 1.70-3.05) compared to women with adequate GWG. The observed increased risk was similar for mild-, severe- and late-onset preeclampsia. No association was found for early-onset preeclampsia. Overweight/obese women with excessive GWG had the highest risk of developing preeclampsia compared to normal weight women with no excessive weight gain (OR = 3.78; 95%CI: 2.65-5.41). CONCLUSIONS: Our results suggested that pre-pregnancy BMI and GWG are independent risk factors for preeclampsia and that the risk might vary by preeclampsia subtypes. Our study also proposed a potential synergistic effect of pre-pregnancy BMI and GWG that warrants further investigation.

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.