Study of the expression levels of Hepatocyte nuclear factor 4 alpha and 3 beta in patients with different outcome of HBV infection

Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3β) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4α and HNF3β with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4α and HNF3β expression were detected by immunohistochemistry. The expression of HNF4α was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3β was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4α was different in patients with different outcome of HBV infection, high expression level of HNF4α may correlate with occurrence of SH

ER Stress Negatively Modulates the Expression of the miR-199a/214 Cluster to Regulates Tumor Survival and Progression in Human Hepatocellular Cancer

Background: Recent studies have emphasized causative links between microRNAs (miRNAs) deregulation and tumor development. In hepatocellular carcinoma (HCC), more and more miRNAs were identified as diagnostic and prognostic cancer biomarkers, as well as additional therapeutic tools. This study aimed to investigate the functional significance and regulatory mechanism of the miR-199a2/214 cluster in HCC progression. Methods and Findings: In this study, we showed that miR-214, as well as miR-199a-3p and miR-199a-5p levels were significantly reduced in the majority of examined 23 HCC tissues and HepG2 and SMMC-7721 cell lines, compared with their nontumor counterparts. To further explore the role of miR-214 in hepatocarcinogenesis, we disclosed that the ER stressinduced pro-survival factor XBP-1 is a target of miR-214 by using western blot assay and luciferase reporter assay. Reexpression of miR-214 in HCC cell lines (HepG2 and SMMC-7721) inhibited proliferation and induced apoptosis. Furthermore, ectopic expression of miR-214 dramatically suppressed the ability of HCC cells to form colonies in vitro and to develop tumors in a subcutaneous xenotransplantation model of the BALB/c athymic nude mice. Moreover, reintroduction of XBP-1s attenuated miR-214-mediated suppression of HCC cells proliferation, colony and tumor formation. To further understand the mechanism of the miR-199a/214 cluster down-expression in HCC, we found that thapsigargin (TG) and tunicamycin (TM) or hypoxia-induced unfolded protein response (UPR) suppresses the expression of the miR-199a/21

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Estimation of aerosol properties over the Chinese desert region with MODIS AOD assimilation in a global model

A Local Ensemble Transform Kalman Filter assimilation system has been implemented into an aerosol-coupled global nonhydrostatic model to simulate the aerosol mass concentration and aerosol optical properties of 3 desert sites (Ansai, Fukang, Shapotou) in northwestern China. One-month experiment results of April 2006 reveal that the data assimilation can correct the much overestimated aerosol surface mass concentration, and has a strong positive effect on the aerosol optical depth (AOD) simulation, improving agreement with observations. Improvement is limited with the Ångström Exponent (AE) simulation, except for much improved correlation coefficient and model skill scores over the Ansai site. Better agreement of the AOD spatial distribution with the independent observations of Terra (Deep Blue) and Multi-angle Imaging Spectroradiometer (MISR) AODs is obtained by assimilating the Moderate Resolution Imaging Spectroradiometer (MODIS) AOD product, especially for regions with AODs lower than 0.30. This study confirms the usefulness of the remote sensing observations for the improvement of global aerosol modeling

Estimation of aerosol properties over the Chinese desert region with MODIS AOD assimilation in a global model

A Local Ensemble Transform Kalman Filter assimilation system has been implemented into an aerosol-coupled global nonhydrostatic model to simulate the aerosol mass concentration and aerosol optical properties of 3 desert sites (Ansai, Fukang, Shapotou) in northwestern China. One-month experiment results of April 2006 reveal that the data assimilation can correct the much overestimated aerosol surface mass concentration, and has a strong positive effect on the aerosol optical depth (AOD) simulation, improving agreement with observations. Improvement is limited with the Ångström Exponent (AE) simulation, except for much improved correlation coefficient and model skill scores over the Ansai site. Better agreement of the AOD spatial distribution with the independent observations of Terra (Deep Blue) and Multi-angle Imaging Spectroradiometer (MISR) AODs is obtained by assimilating the Moderate Resolution Imaging Spectroradiometer (MODIS) AOD product, especially for regions with AODs lower than 0.30. This study confirms the usefulness of the remote sensing observations for the improvement of global aerosol modeling

Mir30c Is Involved in Diabetic Cardiomyopathy through Regulation of Cardiac Autophagy via BECN1

Multiple factors have been shown to promote the progression of diabetic cardiomyopathy. A link has previously been found between Mir30 and autophagy in cancer cells and in the heart, but the role of Mir30 in diabetic heart has not been studied. Using in vitro and in vivo approaches, we found that the depletion of Mir30c and induction of BECN1 enhanced autophagy in diabetic (db/db) hearts and in cardiomyocytes treated with the fatty acid palmitate. We verified that Mir30c repressed BECN1 expression by direct binding to the BECN1 3′ UTRs. Mir30c overexpression inhibited the induction of BECN1 and subsequent autophagy in diabetic hearts and improved cardiac function and structure in diabetic mice. However, these effects were abrogated by BECN1 overexpression. Similarly, Mir30c knockdown resulted in increased BECN1 levels and autophagic flux, aggravating cardiac abnormalities. We also show that SP1, an important transcriptional factor in energy metabolism regulation, is a key upstream activator of Mir30c that binds the promoter region of Mir30c. Our findings indicate that downregulation of Mir30c and subsequent activation of BECN1 promotes autophagy, contributing to the pathogenesis of diabetic cardiomyopathy. This observation suggests a theoretical ground for developing microRNA-based therapeutics against diabetic cardiomyopathy by inhibiting autophagy

Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and <it>pgk</it> promoter: an <it>in vitro</it> and <it>in vivo</it> study

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A) may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (<it>AFP</it>) promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the <it>AFP</it> promoter. It has been shown that linking the <it>AFP</it> enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (<it>pgk</it>) gene can generate a strong and HCC-selective promoter.</p> <p>Methods</p> <p>We constructed a HCC-specific gene therapy system to target PP2A using the <it>AFP</it> enhancer/<it>pgk</it> promoter, and evaluated the efficiency and specificity of this system both <it>in vitro</it> and <it>in vivo</it>.</p> <p>Results</p> <p><it>AFP</it> enhancer/<it>pgk</it> promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B), but did not affect AFP-negative human hepatoma cells (SK-HEP-1) or normal human liver cells (L-02). Moreover, <it>AFP</it> enhancer/<it>pgk</it> promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors.</p> <p>Conclusions</p> <p>The novel approach of <it>AFP</it> enhancer/<it>pgk</it> promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC.</p