Soy isoflavone reduces LPS-induced acute lung injury via increasing aquaporin 1 and aquaporin 5 in rats.

Acute lung injury (ALI) followed with severe inflammation and oxidative stress. Anti-inflammatory and antioxidant are the properties of aquaporin 1 (AQP1) and aquaporin 5 (AQP5). The goal of this study was to see if soy isoflavone can diminish lipopolysaccharide (LPS)-induced ALI and the underling mechanism. LPS-induced ALI was given to Sprague-Dawley rats 14 days following oophorectomy. One hour before the LPS challenge, estradiol (1 mg/kg) was administered subcutaneously as positive control and soy isoflavone was intragastric administration for 14 days prior to LPS challenge with different doses. Six hours after LPS challenge, the pulmonary edema, pathophysiology, inflammation, and the oxidative stress in lung tissues of rats were discovered. We found that soy isoflavone can reduce pulmonary edema and the lung pathology in a dose-dependent manner. Furthermore, tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6 were decreased in rats treated with soy isoflavone. Meanwhile, soy isoflavone reduced pulmonary oxidative stress by decreasing malondialdehyde levels, while increasing superoxide dismutase levels in lung tissues in a dose-dependent manner. Mechanically, we found that the mRNA and protein level of AQP1 and AOP5 were increased in lung tissues of rats treated with soy isoflavone compared the LPS-treated rats. Thus, soy isoflavone alleviates LPS-induced ALI through inducing AQP1 and AQP5.

Prognostic value of high-resolution magnetic resonance imaging in evaluating carotid atherosclerotic plaque in patients with ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a devastating occurrence affecting millions worldwide. This study aimed to evaluate the prognostic value of high-resolution magnetic resonance imaging (HRMRI) in assessing carotid atherosclerotic plaque in IS patients. METHODS: Between January 2013 and March 2015, 338 IS patients were recruited for the investigative purposes of the study. All participants of the study underwent an HRMRI inspection procedure after being admitted into the hospital. During this study, we systematically analyzed and measured various types of fibrous caps, lipid compositions, and plaque lipid ratios. Univariate and multivariate logistic regression analyses were performed for predicting prognosis of IS patients. A receiver-operating characteristic (ROC) curve was employed to determine the accuracy of the IS prognosis. RESULTS: The percentage of type I fibrous caps exhibited significant decrease, while the percentage of type III fibrous caps, lipid compositions, and lipid ratios all displayed increase. The results of the univariate analysis indicated that age, hypertension, hyperlipidemia, treatment regimens, fibrous cap type, plaque type, lipid composition, and lipid ratio shared a correlation in regards to the poor prognosis of IS patients. Multivariate logistic regression analysis demonstrated that the prognosis of IS patients was not necessarily dependent on fibrous cap type, plaque type, or age. ROC curves revealed that the HRMRI possessed a strong predicative ability in relation to the identification of the prognosis of IS patients through factors such as type of plaque and fibrous caps determination. CONCLUSION: Our study conclusively intimated the promise of HRMRI as an evaluative tool for the determination of carotid atherosclerotic plaques in patients with IS.

The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells.

Hepatitis B virus X protein (HBx) is implicated in the pathogenesis of hepatocellular carcinoma, which has been found to be associated with Notch and NF-κB signaling. This study aimed to investigate the crosstalk between Notch and NF-κB pathways in HBx-related hepatocellular carcinoma. An HBx-transformed non-tumor hepatic cell line L02 (L02/HBx) was previously established. Immunofluorescence assays were performed to visualize HBx and the Notch intracellular domain (NICD) in cell nuclei. Co-immunoprecipitation assays were used to investigate physical interactions between HBx and components of the Notch signaling pathway (NICD and JAG1), NF-κB signaling pathway (p65 and p50) or IκBα. L02/HBx cells were treated with the Notch signal inhibitor DAPT or Notch1 siRNA to inhibit the Notch1 pathway. qRT-PCR was used to quantify the expression of the p65, p50 and IκBα genes. Protein expression changes in cytoplasm and nuclei after treatment with DAPT or Notch1 siRNA were analyzed by western blotting and EMSA assays. We found that HBx directly regulated Notch1 signaling, which cross-talked with the NF-κB pathway. Downregulation of Notch1 decreased the binding of NF-κB p65 to its target gene promoter, reduced NF-κB expression and enhanced IκBα expression. The results suggest that HBx functions through the Notch signaling pathway; Notch contributes to hepatocarcinogenesis partially by regulating the NF-κB pathway. Our findings provide new insights into the role of Notch and NF-κB signaling in the progression of hepatocellular carcinoma related to HBx.

Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells.

Hepatocellular carcinoma (HCC) is a malignant tumor and hepatitis B virus X protein (HBx) plays a crucial role in its pathogenesis. The Notch1 signaling pathway is involved in various malignant tumors including liver cancers and down-regulation of Notch-1 may exert anti-tumor effects. Here, we demonstrate that inhibition of Notch1 by plasmid-based shRNA suppresses growth of human hepatic cells transfected with HBx through G0/G1 cell cycle arrest and apoptosis inhibition, possibly linked to the promoted expression of cyclin-dependent kinase inhibitor, P16, and decreased expression of apoptosis inhibitor, Bcl-2. The anti-proliferative and pro-apoptotic effects of Notch1 shRNA in HBx-transformed L02 cell may be partly mediated by down-regulation of nuclear factor-kappaB (NF-κB) binding activities, demonstrating possible cross-talk between Notch-1 and NF-κB signaling pathways. The oncogene HBx may therefore induce malignant transformation of human hepatic cells via Notch1 pathway, indicating that Notch1 plays a crucial role in HBx-related liver cancer and could be an effective therapeutic target for HCC.

Hepatitis B virus X protein promotes the growth of hepatocellular carcinoma by modulation of the Notch signaling pathway.

Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma (HCC), however, little is known about the mechanism. Here, we investigated the relationship between HBx and Notch signaling in HepG2 cells after they were transfected with the HBx gene. It was found that HBx upregulated the expression of Notch-1, Jagged-1 and Hes-1 at the transcriptional level by binding to the Notch-1 intracellular domain, which is congruent with the observations of enhanced malignant biological activities of HBx-transfected HepG2 cells compared with normal HepG2 cells. However, while Notch signaling was blocked, the HBx-induced abnormalities were partially reversed. These findings suggest that HBx may promote the progression of HCC via the activated Notch pathway.

Activated Notch signaling is required for hepatitis B virus X protein to promote proliferation and survival of human hepatic cells.

Hepatitis B virus X protein (HBx) is a multifunctional oncoprotein which plays a crucial role in the pathogenesis of hepatocellular carcinoma (HCC). However, the exact mechanisms remain controversial. Here we show that HBx strongly stimulated cell growth, promoted cell cycle progression and inhibited apoptosis of human non-tumor hepatic cell line L02 cells. It also accelerated tumor formation of L02 cells in BALB/c nude mice. Furthermore, Notch signaling components were upregulated in HBx-expressing L02 cells compared to normal L02 cells. However, blocking Notch signaling with a γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) attenuated cell growth, shortened the S phase of cell cycle and promoted apoptosis of HBx-expressing L02 cell in a dose- and time-dependent manner, but normal L02 cells were not significantly affected by Notch signaling blocking. Therefore, our findings demonstrate that HBx could promote the growth of human non-tumor hepatic cell line L02 cells both in vitro and in vivo, which may require the activation of Notch signaling pathway.