Dalian Medical University

About: Dalian Medical University is a education organization based out in Dalian, China. It is known for research contribution in the topics: Cancer & Apoptosis. The organization has 15623 authors who have published 9993 publications receiving 164145 citations.

Core Fucosylation of the T Cell Receptor Is Required for T Cell Activation.

Abstract: CD4+ T cell activation promotes the pathogenic process of systemic lupus erythematosus (SLE). T cell receptor (TCR) complex are highly core fucosylated glycoproteins, which play important roles in T cell activation. In this study, we found that the core fucosylation of CD4+ T cells was significantly increased in SLE patients. Loss of core fucosyltransferase (Fut8), the sole enzyme for catalyzing the core fucosylation of N-glycan, significantly reduced CD4+ T cell activation and ameliorated the experimental autoimmune encephalomyelitis-induced syndrome in Fut8-/- mice. T cell activation with OVA323-339 loaded major histocompatibility complex II (pMHC-II) on B cell was dramatically attenuated in Fut8-/-OT-II CD4+ T cells compared with Fut8+/+OT-II CD4+ T cells. Moreover, the phosphorylation of ZAP-70 was significantly reduced in Fut8+/+OT-II CD4+ T cells by the treatment of fucosidase. Our results suggest that core fucosylation is required for efficient TCR-pMHC-II contacts in CD4+ T cell activation, and hyper core fucosylation may serve as a potential novel biomarker in the sera from SLE patients.

Control of Matrix Stiffness Using Methacrylate-Gelatin Hydrogels for a Macrophage-Mediated Inflammatory Response.

Abstract: The successful tissue integration of a biomedical material is mainly determined by the inflammatory response after implantation. Macrophage behavior toward implanted materials is pivotal to determine the extent of the inflammatory response. Hydrogels with different properties have been developed for various biomedical applications such as wound dressings or cell-loaded scaffolds. However, there is limited investigation available on the effects of hydrogel mechanical properties on macrophage behavior and the further host inflammatory response. To this end, methacrylate-gelatin (GelMA) hydrogels were selected as a model material to study the effect of hydrogel stiffness (2, 10, and 29 kPa) on macrophage phenotype in vitro and the further host inflammatory response in vivo. Our data showed that macrophages seeded on stiffer surfaces tended to induce macrophages toward a proinflammatory (M1) phenotype with increased macrophage spreading, more defined F-actin and focal adhesion staining, and more proinflammatory cytokine secretion and cluster of differentiation (CD) marker expression compared to those on surfaces with a lower stiffness. When these hydrogels were further subcutaneously implanted in mice to assess their inflammatory response, GelMA hydrogels with a lower stiffness showed more macrophage infiltration but thinner fibrotic capsule formation. The more severe inflammatory response can be attributed to the higher percentage of M1 macrophages induced by GelMA hydrogels with a higher stiffness. Collectively, our data demonstrated that macrophage behavior and the further inflammatory response are mechanically regulated by hydrogel stiffness. The macrophage phenotype rather than the macrophage number predominately determined the inflammatory response after the implantation, which can provide new insights into the future design and application of novel hydrogel-based biomaterials.

Clinicopathological and prognostic significance of FOXP3+ tumor infiltrating lymphocytes in patients with breast cancer: a meta-analysis

Abstract: The prognostic significance of FOXP3+ tumor-infiltrating lymphocytes (TILs) in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic significance in patients with breast cancer. PubMed, Embase, Cochrane Database and the Ovid Database were systematically searched (up to April 2015). The meta-analysis was performed using hazard ratio (HR), odds ratio (OR) and 95 % confidence intervals (CI) as effect measures. Using the random-effects model, statistical analysis was performed using Stata software, version 12.0. Seventeen studies including 8277 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of FOXP3+ TILs was significant when comparing the lymph node positive group to negative group (OR = 1.305, 95 % CI [1.071, 1.590]), the histological grade III group to the I–II group (OR = 3.067, 95 % CI [2.288, 4.111]), the ER positive group to the negative group (OR = 0.435, 95 % CI [0.287, 0.660]), the PR positive group to the negative group (OR = 0.493, 95 % CI [0.296, 0.822]), the HER2 positive group to the negative group (OR = 1.896, 95 % CI [1.335, 2.692]), the TNBC group to the non TNBC group (OR = 2.456, 95 % CI [1.801, 3.348]). The detection of FOXP3+ TILs was significantly correlated with the recurrence-free survival (RFS) of patients (HR = 1.752, 95 % CI [1.188–2.584]) and the overall survival (OS) of patients (HR =1.447, 95 % CI [1.037–2.019]). Our meta-analysis demonstrates that the presence of high levels of FOXP3+ TILs is associated with prognosis for breast cancer patients and predicts lymph node metastasis, hormone receptor and HER-2 status.