Salvianolic Acid B Inhibits Activation of Human Primary Hepatic Stellate Cells Through Downregulation of the Myocyte Enhancer Factor 2 Signaling Pathway

Various isoforms of myocyte enhancer factor 2 (MEF2) have been shown to play a role in the activation of rat hepatic stellate cells (HSCs) in culture. The signals that regulate MEF2 in HSCs are unknown. In addition, whether MEF2s regulate the activation of human HSCs (H-HSCs) is unclear. Here, we studied the expression and function of MEF2s in H-HSCs. Our data showed that the levels of MEF2A, C, and D proteins were high in liver tissues from patients with cirrhosis and increased during culture-induced activation of primary H-HSCs. Exposure of H-HSCs to transforming growth factor beta 1 (TGF-β1) led to a significant increase in MEF2A and C protein levels and enhanced MEF2 activity. Interestingly, TGF-β1 did not further enhance MEF2D levels. Furthermore, TGF-β1 activated p38 mitogen-activated protein kinase (MAPK) and led to increased phosphorylation of MEF2C at its p38 recognition site. Inhibition of p38 MAPK inhibited both TGF-β1- and culture-induced activation of MEF2. The activity of collagen I reporter in H-HSCs was significantly reduced when MEF2A and MEF2C were blocked with overexpression of dominant negative MEF2 mutants. Salvianolic-acid B (SA-B), a water-soluble element of Salvia miltiorrhiza known to have anti-fibrosis effects, attenuated both basal and TGF-β1-induced increased levels of MEF2A and C mRNA and protein. In addition, SA-B inhibited MEF2 activity, which correlated with reduced expression of the HSC activation markers, α-smooth muscle actin (α-SMA), and collagen I. Administration of SA-B reduced MEF2A in vivo, which was accompanied by reduced levels of α-SMA in a model of dimethylnitrosamine-induced rat liver fibrosis. We concluded that the MEF2 transcription factor was stimulated by TGF-β1 in H-HSCs. Antagonizing TGF-β1-induced activation of the MEF2 signaling pathway may account in part for the anti-fibrosis effects of SA-B

Effect of Fuzheng Huayu formula and its actions against liver fibrosis

Liver fibrosis is a common histological process to develop into cirrhosis in various chronic liver diseases including chronic hepatitis and fatty liver. Therefore anti-liver fibrosis is very important strategy to treat chronic liver diseases. Fuzheng Huayu (FZHY), a preparation containing herbs such as Radix Salvia Miltiorrhizae, Cordyceps, Semen Persicae, was formulated on the basis of Chinese medicine theory in treating liver fibrosis and was approved. Pharmacological studies and clinical trials demonstrate that FZHY has a significant effect against liver fibrosis and that many of the pharmacological actions are attributable to the effect. This article reviews the effects and actions of FZHY, in particular the effects observed from clinical trials in treating liver fibrosis caused by chronic hepatitis B and the actions on inhibition of hepatic stellate cell activation, protection of hepatocytes and inhibition of hepatic sinusoidal capillarization. This article also reviews the coordinated effects of the constituent herbs of FZHY and the actions of their active compounds such as salvianonic acid B (SA-B) on liver fibrosis

A Randomized Controlled Study of Fuzheng Huayu Capsule for Prevention of Esophageal Variceal Bleeding in Patients with Liver Cirrhosis

To elucidate the role of Fuzheng Huayu Capsule, a herbal formula, in the prevention of esophageal variceal bleeding in cirrhotic patients, a multicenter randomized and placebo-controlled trial was carried out. One hundred forty-six cirrhotic patients with esophageal varices were enrolled to compare the probability of upper gastrointestinal bleeding and survival between Fuzheng Huayu Capsule group and controlled group for the duration of 2 years. The results demonstrated that the FZHYC could effectively reduce the risk of variceal bleeding and improve survival rates for cirrhotic patients with varices, especially the combination of the capsule and Propranolol, which presented a better effect; FZHYC could reduce the varices size in patients with small ones. Its effect may be related to the amelioration of hepatic fibrosis.</jats:p

OsPIE1, the Rice Ortholog of Arabidopsis PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1, Is Essential for Embryo Development

orthologs in monocots remains unknown., respectively).Taken together, our results suggest that OsPIE1 is the rice ortholog of Arabidopsis PIE1 and plays an essential role in rice embryo development

Challenging the Invisible Web

The revolution of the World Wide Web (WWW or Web) has set off the globalization of information publishing and access. Organizations, enterprises, and individuals produce and update data on the Web everyday. With the explosive growth of information on the WWW, it becomes more and more difficult for users to accurately find and completely retrieve what they want. Although there are hundreds of thousands of general-purpose and special-purpose search engines and search tools, most users still find it hard to retrieve information precisely. Moreover, considering the great amount of valuable information hidden in the Invisible Web that is generally inaccessible to traditional "crawlers", providing users with an effective and efficient tool for Web searching is necessary and urgent. First, this dissertation proposes an adaptive data model for meta-search engines (ADMIRE) that can be used to formally and meticulously describe the user interfaces and query capabilities of heterogeneous search engines on the Internet. Compared with related work, this model focuses more on the constraints between the terms, term modifiers, attribute order, and the impact of logical operators. Second, this dissertation presents a constraint-based query translation algorithm. When translating a query from a meta-search engine to a remote source, the mediator considers the function and position restrictions of terms, term modifiers and logical operators among the controls in the user interfaces to the underlying sources sufficiently, thus allowing the meta-search engine to utilize the query capabilities of the specific sources as far as possible. In addition, a two-phase query subsuming mechanism is put forward to compensate for the functional discrepancies between sources, in order to make a more accurate query translation. Furthermore, this dissertation presents a mechanism for constructing adaptive, dynamically generated user interfaces for meta-search engines based on the above-mentioned model. The concept of control constraint rules has been proposed and applied to the user interface construction. Depending on the state of interaction between users and system, such meta-search engines adapt their interfaces to the concrete user interfaces of differing kinds of search engines (Boolean model with differing syntax, vector-space/probabilistic model, natural language support, etc.), so as to overcome the constraints of heterogeneous search engines and utilize the functionality of the individual search engines as much as possible. Finally, this dissertation also tackles some issues on wrapper generation and result merging for Web information sources. The experiments show that an information integration system with an adaptive, dynamically generated user interface, coordinating the constraints among the heterogeneous sources, will greatly improve the effectiveness of integrated information searching, and will utilize the query capabilities of sources as far as possible. The adaptive meta-search engine architecture proposed in this dissertation has been applied to the information integration of scientific publications-oriented search engines. It can also be applied to other generic domains or specific domains of information integration, such as integrating all kinds of WWW search engines (or search tools) and online repositories with quite different user interfaces and query models. With the help of source wrapping tools, they can also be used to integrate queryable information sources delivering semi-structured or non-structured data, such as product catalogues, weather reports, software directories, and so on

Down-regulation of PM20D1 is associated with clinics outcomes and prognosis of gestational patients with diabetes mellitus

IntroductionTo investigate clinic role of PM20D1 in gestational diabetes mellitus (GDM).Material and methodsThis observational study included 189 cases of GDM patients who came to our department during March 2018 to December 2019. Additionally, 100 healthy pregnant individuals who came to physical examination were included as healthy control during the same period. Western blotting was used to determine the expression of PM20D1 at gestational age 24-28 weeks, as well as gestational age 37-40 weeks. Serum inflammatory factors of C reactive protein (CRP), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α.ResultsThe expression of PM20D1 was markedly decreased in GDM patients compared with the healthy control. Besides, patients of third trimester of pregnancy (gestational age 37-40 weeks) showed significantlylower expression of PM20D1 than patients of second trimester of pregnancy (gestational age 24-28 weeks). Serum levels of CRP, IL-1β, IL-6, TNF-α and leptin were remarkably higher and levels of adiponectin were markedly lower in GDM patients at both second and third trimester of pregnancy, which were the highest at third trimester of pregnancy. Pearson’s analysis showed PM20D1 was negatively correlated with IL-1β, IL-6 and leptin and positively correlated with adiponectin. At second trimester of pregnancy, patients with lower expression of PM20D1 showed remarkably higher levels of HOMA-IR, fasting insulin, FBG, OGTT-1hPG, OGTT-2hPG, as well as TG and LDL-ch, as well as markedly lower levels of HDL-ch. Down-regulated PM20D1 predicted poor pregnancy outcomes.ConclusionsReduced was PM20D1 associated with patients’ clinics outcomes and pregnancy outcomes in GDM.</jats:sec