Chronic stress induces steatohepatitis while decreases visceral fat mass in mice

BACKGROUND: Prolonged stress leads over time to allostatic load on the body and is likely to exacerbate a disease process. Long-term of stress exposure is one of a risk factor for metabolism-related diseases such as obesity and type 2 diabetes. However, the relationship between chronic stress and non-alcoholic fatty liver disease (NAFLD) remain unknown. METHODS: To address the hypothesis that chronic stress associate to NAFLD development, we subjected C57bl/6 mice to electric foot shock and restraint stress for 12 weeks to set up chronic stress model. Then the serum and hepatic triglyceride (TG), total cholesterol (TC) were measured. Hepatic HE and Oil red O staining were used to specify the state of the NAFLD. To investigate whether inflammation takes part in the stress-induced NAFLD process, related visceral fat, serum and hepatic inflammatory factors were measured. RESULTS: We observed that chronic stress led to an overall increase of hepatic triglyceride and cholesterol while decreasing body weight and visceral fat mass. Microvesicular steatosis, lobular inflammation and ballooning degeneration were seen in stress liver section. This effect was correlated with elevated hepatic and serum inflammatory factors. Although the amount of visceral fat was decreased in stress group, various adipocytokines were elevated. CONCLUSIONS: We showed that chronic stress is associated to NAFLD and chronic inflammation in visceral fat, though food intake and visceral fat mass were decreased. These results may contribute to better understanding of the mechanism from steatosis to steatohepatitis, and propose a novel insight into the prevention and treatment of NAFLD

Molecular Analysis of Spring Viraemia of Carp Virus in China: A Fatal Aquatic Viral Disease that Might Spread in East Asian

Spring viraemia of carp (SVC) is a fatal viral disease for cyprinid fish, which is caused by spring viraemia of carp virus (SVCV). To date, no SVC outbreak has been reported in China. Between 1998 and 2002, outbreaks of SVC were reported in ornamental and wild fish in Europe and America, imported from multiple sources including China. Based on phylogenetic analysis, the viral strain isolated from America was shown to be originated from Asia. These outbreaks not only resulted in huge economic losses, but also raise an interesting question as to whether SVCV really exists in China and if so, is it responsible for SVC outbreaks? From 2002 to 2006, we screened 6700 samples from ornamental fish farms using the cell culture method of the Office International des Epizooties (OIE), and further verified the presence of SVCV by ELISA and real-time quantitative RT-PCR. Two infected samples were found and the complete genome of SVCV was sequenced from one of the isolates, termed SVCV-C1. Several unique hallmarks of SVCV-C1 were identified, including six amino acid (KSLANA) insertion in the viral RNA-dependent RNA polymerase (L) protein and ten nucleotide insertion in the region between glycoprotein (G) and L genes in European SVCV strains. Phylogenetic tree analysis of the full-length G protein of selected SVCV isolates from the United Kingdom and United States revealed that G proteins could be classified into Ia and Id sub genogroups. The Ia sub genogroup can be further divided into newly defined sub genogroups Ia-A and Ia-B. The isolates derived from the United States and China including the SVCV-C1 belongs to in the Ia-A sub genogroup. The SVCV-C1 G protein shares more than 99% homology with the G proteins of the SVCV strains from England and the United States, making it difficult to compare their pathogenicity. Comparison of the predicted three-dimensional structure based on the published G protein sequences from five SVCV strains revealed that the main differences were in the loops of the pleckstrin homology domains. Since SVCV is highly pathogenic, we speculate that SVC may therefore pose a serious threat to farmed cyprinid fish in China

MicroRNA roles in beta-catenin pathway

β-catenin, a key factor in the Wnt signaling pathway, has essential functions in the regulation of cell growth and differentiation. Aberrant β-catenin signaling has been linked to various disease pathologies, including an important role in tumorigenesis. Here, we review the regulation of the Wnt signaling pathway as it relates to β-catenin signaling in tumorigenesis, with particular focus on the role of microRNAs. Finally, we discuss the potential of β-catenin targeted therapeutics for cancer treatment

A Novel Selective Ensemble Algorithm for Imbalanced Data Classification Based on Exploratory Undersampling

Learning with imbalanced data is one of the emergent challenging tasks in machine learning. Recently, ensemble learning has arisen as an effective solution to class imbalance problems. The combination of bagging and boosting with data preprocessing resampling, namely, the simplest and accurate exploratory undersampling, has become the most popular method for imbalanced data classification. In this paper, we propose a novel selective ensemble construction method based on exploratory undersampling, RotEasy, with the advantage of improving storage requirement and computational efficiency by ensemble pruning technology. Our methodology aims to enhance the diversity between individual classifiers through feature extraction and diversity regularized ensemble pruning. We made a comprehensive comparison between our method and some state-of-the-art imbalanced learning methods. Experimental results on 20 real-world imbalanced data sets show that RotEasy possesses a significant increase in performance, contrasted by a nonparametric statistical test and various evaluation criteria

Downregulation of KLF8 expression by shRNA induces inhibition of cell proliferation in CAL27 human oral cancer cells

Objectives: KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. Study Design: We developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral cancer cells. Downregulation of KLF8 was confirmed by evaluating GFP expressions, RT-PCR and western blot analysis. Finally, the effects of KLF8 downregulation were analyzed by MTT assay and colony formation assays. Results: The expression levels of KLF8 mRNA and proteins are reduced in CAL 27 cells that transfected with 21- nt siRNA against KLF8. Lentivirus-mediated silencing of KLF8 reduces cell proliferation and colonies number, thereby indicating the role of KLF8 in cell proliferation and tumorigenesis. Conclusions: These results strongly suggest that KLF8 is essential for growth of CAL 27 cancer cells. A better understanding of KLF8 function and processing may provide novel insights into the clinical therapy of oral cancer

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.</p> <p>Results</p> <p>Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.</p> <p>Conclusion</p> <p>To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.</p