High-Level Expression of Notch1 Increased the Risk of Metastasis in T1 Stage Clear Cell Renal Cell Carcinoma

Background: Although metastasis of clear cell renal cell carcinoma (ccRCC) is basically observed in late stage tumors, T1 stage metastasis of ccRCC can also be found with no definite molecular cause resulting inappropriate selection of surgery method and poor prognosis. Notch signaling is a conserved, widely expressed signal pathway that mediates various cellular processes in normal development and tumorigenesis. This study aims to explore the potential role and mechanism of Notch signaling in the metastasis of T1 stage ccRCC. Methodology/Principal Findings: The expression of Notch1 and Jagged1 were analyzed in tumor tissues and matched normal adjacent tissues obtained from 51 ccRCC patients. Compared to non-tumor tissues, Notch1 and Jagged1 expression was significantly elevated both in mRNA and protein levels in tumors. Tissue samples of localized and metastatic tumors were divided into three groups based on their tumor stages and the relative mRNA expression of Notch1 and Jagged1 were analyzed. Compared to localized tumors, Notch1 expression was significantly elevated in metastatic tumors in T1 stage while Jagged1 expression was not statistically different between localized and metastatic tumors of all stages. The average size of metastatic tumors was significantly larger than localized tumors in T1 stage ccRCC and the elevated expression of Notch1 was significantly positive correlated with the tumor diameter. The functional significance of Notch signaling was studied by transfection of 786-O, Caki-1 and HKC cell lines with full-length expression plasmids of Notch1 and Jagged1

A fusion protein of vimentin with Fc fragment inhibits Japanese encephalitis virus replication

Japanese encephalitis virus (JEV), a member of the Flaviviridae family and a flavivirus, is known to induce acute encephalitis. Vimentin protein has been identified as a potential receptor for JEV, engaging in interactions with the viral membrane protein. The Fc fragment, an integral constituent of immunoglobulins, plays a crucial role in antigen recognition by dendritic cells (DCs) or phagocytes, leading to subsequent antigen presentation, cytotoxicity, or phagocytosis. In this study, we fused the receptor of JEV vimentin with the Fc fragment of IgG and expressed the resulting vimentin-Fc fusion protein in Escherichia coli. Pull-down experiments demonstrated the binding ability of the vimentin-Fc fusion protein to JEV virion in vitro. Additionally, we conducted inhibition assays at the cellular level, revealing the ability of vimentin-Fc protein suppressing JEV replication, it may be a promising passive immunotherapy agent for JEV. These findings pave the way for potential therapeutic strategies against JEV

Overexpression of E2F1 promotes tumor malignancy and correlates with TNM stages in clear cell renal cell carcinoma.

BACKGROUND: Transcription factor E2F1 exerts effects on many types of cancers. As an upstream regulator of a host of genes, E2F1 can trigger diverse aberrant transcription processes that may dominate malignancy. Clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinoma which displays high malignancy and has a shortage of biomarkers in clinics. Our study aimed to explore the function of E2F1 in ccRCC and its correlation with clinicopathological parameters. METHODOLOGY/PRINCIPLE FINDINGS: Transcription factor E2F1 was mainly distributed in cancer cell nucleus and mRNA expression significantly increased in 72 cases of clear cell renal cell carcinoma (ccRCC) tissues compared with adjacent non-cancerous kidney tissues (p<0.001). The protein expression was consistent with mRNA expression. Further analysis in 92 cases indicated that E2F1 mRNA level expression was associated with the tumor pathologic parameters embracing diameter, Fuhrman tumor grade, pT stage, TNM stage grouping and macrovascular infiltration (MAVI). These surgical specimens had high grade tumors accompanied with an elevated E2F1 expression. Moreover, E2F1 transfection was found to contribute significantly to cancer cell proliferation, migration and invasion in vitro. CONCLUSIONS/SIGNIFICANCE: Overexpression of E2F1 may be a key event in the local and vascular infiltration of ccRCC indicated by the activation of matrix metalloproteinase (MMP) 2 and MMP9. These findings highlighted the implication of E2F1's function in the metastatic process. Furthermore, the clinical relevance of E2F1 in ccRCC pointed to a potential new therapeutic target

Risk of Obstructive Sleep Apnea in Parkinson’s Disease: A Meta-Analysis

<div><p>Study Objectives</p><p>Sleep disorders are a common symptom of Parkinson’s disease (PD) and they significantly impair the sleep quality of the PD patients. However, there is no conclusive evidence to support the relation between PD and the prevalence of obstructive sleep apnea (OSA). The purpose of this meta-analysis review is to evaluate the association between PD and the prevalence of OSA.</p> <p>Methods</p><p>A comprehensive literature search was conducted on PubMed and Embase through July 2013. Only studies that referred to PD and the prevalence of OSA and that met the selection criteria were included in the analysis. The odds ratios (ORs) were used to evaluate the relationship of PD and the prevalence of OSA by the fixed-effect model.</p> <p>Results</p><p>Five eligible studies were analyzed in this study including 322 cases and 6,361 controls. The pooled-analysis showed the OR to be 0.60 (95% confidence interval (CI): 0.44 to 0.81, P = 0.001) and I² = 0.0% (χ² = 3.90, P = 0.420) in the fixed-effect model.</p> <p>Conclusions</p><p>Although we only included five small sample studies that indicated high homogeneity in the heterogeneity test, the results suggest that there is a significant negative association between PD and the prevalence of OSA; PD patients generally have a reduced prevalence of OSA. According to our analysis, these results are primarily due to the lower BMI of PD patients when compared with the general population controls.</p> </div

Flow chart for literature search and screening.

<p>Flow chart for literature search and screening.</p

Notch1 and Jagged1 mRNA expression analysis at different stages in ccRCC samples.

<p>(A) Analysis showing significantly higher expression of Notch1 in metastatic tumors at T1 stage compared to localized tumors(P = 0.001). (B) No statistically significant difference of Jagged1 expression in all three stages. The data shown are mean±SD.</p

Attenuation of Krüppel-Like Factor 4 Facilitates Carcinogenesis by Inducing G1/S Phase Arrest in Clear Cell Renal Cell Carcinoma

<div><p>Krüppel-like factor 4 (KLF4) is a transcription factor with diverse functions in various cancer types; however, the function of KLF4 in clear cell renal cell carcinoma (ccRCC) carcinogenesis remains unknown. In this study, we initially examined KLF4 expression by using a cohort of surgically removed ccRCC specimens and cell lines. Results indicated that the transcription and translation of KLF4 were lower in ccRCC tissues than in patient-matched normal tissues. Furthermore, the KLF4 expression was significantly downregulated in the five ccRCC cell lines at protein and mRNA levels compared with that in normal renal proximal tubular epithelial cell lines (HKC). KLF4 downregulation was significantly correlated with tumor stage and tumor diameter. Promoter hypermethylation may contribute to its low expression. In addition, <i>in vitro</i> studies indicated that the KLF4 overexpression significantly inhibited proliferation in human ccRCC cell lines 786-O and ACHN. Moreover, the KLF4 overexpression arrested the cell cycle progress at the G1/S phase transition by upregulating p21<i>^WAF1/CIP1</i> expression and downregulating cyclin D1 expression, KLF4 knockdown in HKC cells did the opposite. <i>In vivo</i> studies confirmed the anti-proliferative effect of KLF4. Our results suggested that KLF4 had an important function in suppressing the growth of ccRCC.</p> </div

Analysis of cell cycle with over-expression of Notch1 and Jagged1.

<p>(A)–(B) In 786-O, Caki-1 and HKC cell line, cell cycle analysis demonstrating no difference between cells over-expressing Notch1 and Jagged1 compared to controls. (C) P21 and P27 remained unchanged in all cell lines after transfected with Notch1 and Jagged1 plasmids.</p

Notch1 promoting the proliferation in tumor and normal kidney cell lines.

<p>Proliferation assay by MTS showing increased proliferation in Caki-1 and 786-O cell line after Notch1 and Jagged1 expression. MTS assay in HKC cell line showing increased proliferation rate in Notch1 expressing cells only. The data shown are means±SD from two independent experiments, each carried out in triplicate.</p