Iris epithelium is a double-layered pigmented cuboidal epithelium. According to the current model, the neural retina and the posterior iris pigment epithelium (IPE) are derived from the inner wall of the optic cup, while the retinal pigment epithelium (RPE) and the anterior IPE are derived from the outer wall of the optic cup during development. Our current study shows evidence, contradicting this model of fetal iris development. We demonstrate that human fetal iris expression patterns of Otx2 and Mitf transcription factors are similar, while the expressions of Otx2 and Sox2 are complementary. Furthermore, IPE and RPE exhibit identical morphologic development during the early embryonic period. Our results suggest that the outer layer of the optic cup forms two layers of the iris epithelium, and the posterior IPE is the inward-curling anterior rim of the outer layer of the optic cup. These findings provide a reasonable explanation of how IPE cells can be used as an appropriate substitute for RPE cells.
Transforming growth factor ?1 (TGF-?1) and inhibitor of differentiation/DNA-binding 1 (Id-1) have been shown to be associated with aggressive metastatic behavior of cancer cells in many malignant tumors. However, their role in gastric cancer (GC) has not been established. In this study, we investigated the relationship between expression of Id-1 and TGF-?1 in GC as well as their association with GC progression. The immunohistochemical analysis of 71 human GC samples indicated that both Id-1 and TGF-?1 were markedly upregulated in tumor tissue compared with the adjacent tissue; in addition, a significant positive correlation was found between the expression levels of Id-1 and TGF-?1 by Pearson's correlation analysis. Furthermore, the investigation of the association of Id-1 and TGF-?1 with patient clinical characteristics revealed that Id-1 expression was significantly correlated with tumor differentiation, while TGF-?1 was associated with lymph node metastasis. The results were validated in vitro by using a GC cell line, AGS. The expression of Id-1 was upregulated at 24 and 48 h after the treatment with TGF-?1, whereas it did not affect the proliferation of cells. TGF-?1 also influenced the expression of N-cadherin and ?-catenin. Our results suggested that Id-1 and TGF-?1 played important roles in the progression of GC, in which Id-1 might act as a downstream mediator of TGF-?1 signaling through a regulatory mechanism involving N-cadherin and ?-catenin. The TGF-?1/Id-1 axis might serve as a future therapeutic target for GC.
Cognitive deficits are the core symptoms of schizophrenia. Spine deficits have been found in hippocampus of schizophrenia patients, and were associated with cognitive impairments. N-methyl-D-asparate receptors (NMDARs) had been known to play a critical role in synaptic pruning and stabilization during adolescence. In the present study, male adolescent rats were exposed to dizocilpine (MK-801) (0.2mg/kg i.p qd) or 0.9% saline for 14 days. Then spatial memory, spine morphological changes and RhoA, Rac1, Cdc42 mRNA levels in hippocampus were measured. As a result, MK-801 impaired spatial memory in the adolescent rats, as well as reduced the proportion of mushroom spines and increased the proportion of stubby spines in hippocampus. MK-801 also reduced the expression levels of Rac1 and Cdc42 mRNA and upregulated RhoA mRNA in hippocampus. These results imply that subchronic MK-801 administration during adolescence might disturb the expression of RhoA, Rac1 and Cdc42 mRNA, and then lead to the decay of the spines in hippocampus, which could be involved in cognitive impairments in schizophrenia.
The aim of this study was to investigate the prognostic value of chemokine receptor CCR7 expression and intratumoral FOXP3(+) regulatory T cells (Tregs) in gastric cancer. CCR7(+) tumor cells and FOXP3(+) Tregs were assessed by immunohistochemistry in tissue microarrays containing gastric cancer from 133 patients. Prognostic effects of low or high CCR7 and FOXP3 expression were evaluated by Cox regression and Kaplan-Meier analysis, as well as the correlation between CCR7 positive score and intratumoral FOXP3(+) cell number in a longitudinal assessment. The analysis showed that the high expression levels of CCR7 and FOXP3 were detected in 69.9% and 65.4% of cases, respectively. High CCR7 expression in gastric cancer cells was significantly associated with poor overall survival (OS) (P = 0.010) and lymph node metastasis (P = 0.009), and was an independent factor for worse OS (P = 0.023) by multivariate analysis. High numbers of intratumoral FOXP3(+) Tregs significantly correlated with shorter OS (P = 0.021) and lymph node metastasis (P = 0.024), and was also an independent factor for adverse OS (P = 0.035). Furthermore, there was a significantly positive correlation between CCR7 positive score and intratumoral FOXP3(+) cell number (r = 0.949, P<0.001). These results revealed that CCR7 expression in gastric cancer cells and intratumoral FOXP3(+) Tregs could be considered as a co-indicator of clinical prognosis of gastric cancer.
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