ß-arrestin interacts with TRAF6 to negatively regulate the NF-κB pathway in triangle sail mussel Hyriopsis cumingii.

As members of arrestins family, ß-arrestins are widely expressed in monocytes, macrophages, neutrophils and other immune cells. They can regulate the immune response of bodies through various ways. In the present study, a ß-arrestin homolog named Hcß-arrestin was cloned and identified from Hyriopsis cumingii. Predicted Hcß-arrestin protein contained a conserved arrestin domain, which could be further divided into arrestin-N (39-192aa) and arrestin-C (211-365aa). Amino acid sequence alignment showed that it had the highest identity with Mytilus galloprovincialis and Mytilus edulis counterpart, which was 89.02% and 87.68%, respectively. Furthermore, real-time quantitative PCR analysis showed that the Hcß-arrestin gene was widely expressed in the detected tissues and with the highest expression in hepatopancreas. The transcription of Hcß-arrestin in hepatopancreas and gill of mussels was significantly up-regulated after stimulation with peptidoglycan, lipopolysaccharide (LPS) and polyinosinic polycytidylic acid. Knockdown of Hcß-arrestin gene significantly increased the expression of some antibacterial effector genes, such as lysozyme, LPS-binding protein/bactericidal permeability increasing protein and theromacin in hepatopancreas and gills of LPS stimulated mussels, but only had little effect on TLR pathway genes. In addition, GST pull-down assay confirmed that Hcß-arrestin can bind to HcTRAF6 protein in vitro. Dual luciferase reporter assay showed that the co-expression of HcTRAF6 and Hcß-arrestin inhibited the activation of NF-κB reporter by HcTRAF6. These findings indicated that Hcß-arrestins could interact with HcTRAF6 to negatively regulate the NF-κB pathway in H. cumingii.

Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance.

OBJECTIVE: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer (NSCLC) and their clinical significance by observing patient prognosis. METHODS: VEGFR2 and NRP-1 were assessed by immunohistochemistry (IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor (KDR) and NRP-1 copy number gain (CNG) was assessed by fluorescence in situ hybridization (FISH). The distributions of overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test. RESULTS: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG (+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue (χ(2)=11.22, P=0.001; χ(2)=9.82, P=0.001, respectively); similar results were obtained using CNGs (χ(2)=4.39, P=0.036; χ(2)=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status (P<0.05), but not age, gender or pathology type (P>0.05). VEGFR2 showed a strong correlation with NRP-1 (Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG (Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression (P<0.05). CONCLUSIONS: According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis (P<0.05 for OS and PFS). This information will be beneficial for clinical anti-angiogenic treatment in NSCLC.

Global burden of major depressive disorders attributable to intimate partner violence against women: Magnitude, temporal trends, and regional inequalities.

AIMS: This study aimed to analyze the temporal trends, spatial heterogeneities, and potential improvements in the burden of major depressive disorders (MDD) attributable to intimate partner violence (IPV) against women across 21 global burden of disease (GBD) regions, and 204 countries and territories from 1990 to 2019. METHODS: We evaluated the burden of MDD attributable to IPV against women, as measured in disability-adjusted life years (DALYs) per 100,000 people across 21 GBD regions and 204 GBD countries and territories, using data from the 2019 GBD Study. The average annual percentage change (AAPC) of the DALY age-standardized rates (ASRs) was used to reflect trends over time. LOESS and quantile regression were used to model the relationship between the five GBD sociodemographic index (SDI) categories and DALY ASRs. Frontier analysis determined the minimum achievable DALY ASR associated with developmental status, as measured by the SDI. RESULTS: The overall AAPC in age-standardized DALY rates for MDD attributable to IPV declined globally between 1990 and 2019. Despite the overall global decline (AAPC -0.08 [95 % UI -0.2, 0.03]), certain GBD regions, particularly high-income North America and Central Latin America, have experienced increases in DALY ASRs. The relationship between SDI and MDD burden showed a U-shaped variability, with low-SDI regions consistently exhibiting higher and stable DALY rates. Frontier analysis revealed that several countries, regardless of their SDI, have substantial gaps between observed and potentially achievable DALY rates, indicating areas for targeted intervention to reduce the burden of MDD due to IPV. CONCLUSIONS: Significant spatial and temporal heterogeneity in MDD due to IPV was observed globally from 1990 to 2019, highlighting the substantial potential for improvement in various countries. Protective measures should be customized to suit the unique cultural contexts, developmental statuses, and regional disparities of each country.