592 research outputs found
Sequential Wnt Agonist then Antagonist Treatment Accelerates Tissue Repair and Minimizes Fibrosis
Tissue fibrosis compromises organ function and occurs as a potential
long-term outcome in response to acute tissue injuries. Currently, lack of
mechanistic understanding prevents effective prevention and treatment of the
progression from acute injury to fibrosis. Here, we combined quantitative
experimental studies with a mouse kidney injury model and a computational
approach to determine how the physiological consequences are determined by the
severity of ischemia injury, and to identify how to manipulate Wnt signaling to
accelerate repair of ischemic tissue damage while minimizing fibrosis. The
study reveals that Wnt-mediated memory of prior injury contributes to fibrosis
progression, and ischemic preconditioning reduces the risk of death but
increases the risk of fibrosis. Furthermore, we validated the prediction that
sequential combination therapy of initial treatment with a Wnt agonist followed
by treatment with a Wnt antagonist can reduce both the risk of death and
fibrosis in response to acute injuries
Reading Promotion: Conceptual Models and Category Frameworks Analysis
The paper summarizes the practical and theoretical development of reading promotion in various countries in the world and reveals the status of the magnificent practices and active research of reading promotion in China. According to the conceptual object, the existing definitions of reading promotion are divided into the goal-oriented conceptual model and the content-oriented conceptual model . The defining principles and conceptual scopes of these two models are analyzed. Starting with confirming the defining principle and analyzing the scopes of conceptual elements, the definitions of reading promotion and library reading promotion are given. The research is beneficial for librarians to better cognize the conceptual scope of reading promotion and to plan the work
Comparison of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assessment for Her-2 status in breast cancer
<p>Abstract</p> <p>Background</p> <p>The concordance rate between IHC and FISH according to clinical performance is still controversial. We report a prospective study to reflect the concordance between IHC and FISH in Guilin city, People's Republic of China.</p> <p>Methods</p> <p>Fifty cases of invasive ductal carcinoma of breast tested by IHC and scored as 0, 1+, 2+ and 3+ by pathologists were further analyzed by FISH using a commercially available double-color probe, and the FISH findings were compared with IHC test results.</p> <p>Results</p> <p>A total concordance of 82.0% was observed with a Kappa coefficient of 0.640 (P < 0.001). A high discordance was observed in 30.0% of the patients with IHC 2+, 7.1% in IHC 3+, 19.2% overall in IHC 0 and 1+.</p> <p>Conclusion</p> <p>The IHC can be used firstly to screen the HER-2 status, and FISH can be used as a supplementary role to IHC and 2+ and some negative cases. And only those cases with Her-2 status of IHC 3+ or FISH positive should be treated with Herceptin.</p
Complete sequence determination of a novel reptile iridovirus isolated from soft-shelled turtle and evolutionary analysis of Iridoviridae
Fish Cholesterol 25-Hydroxylase Inhibits Virus Replication via Regulating Interferon Immune Response or Affecting Virus Entry
Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-induced gene that catalyzes the oxidation of cholesterol to 25-hydroxycholesterol (25HC), which exerts broad-spectrum antiviral function. To investigate the roles of fish CH25H in Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) infection, we cloned and characterized a CH25H homolog from orange-spotted grouper (Epinephelus coioides) (EcCH25H). EcCH25H encoded a 271-amino-acid polypeptide, with 86 and 59% homology with yellow croaker (Larimichthys crocea) and humans, respectively. EcCH25H contained a conserved fatty acid (FA) hydroxylase domain and an ERG3 domain. EcCH25H expression was induced by RGNNV or SGIV infection, lipopolysaccharide (LPS) or poly (I:C) treatment in vitro. Subcellular localization showed that EcCH25H and mutant EcCH25H-M were distributed in the cytoplasm and partly colocalized with the endoplasmic reticulum. SGIV and RGNNV replication was decreased by EcCH25H overexpression, which was reflected in the reduced severity of the cytopathic effect and a decrease in viral gene transcription, but replication of both viruses was increased by knockdown of EcCH25H. Besides, the antiviral activity was dependent on its enzymatic activity. Treatment with 25HC significantly inhibited replication of SGIV and RGNNV. EcCH25H overexpression positively regulated the IFN-related molecules and proinflammatory cytokines, and increased both IFN and ISRE promoter activities. Moreover, 25HC treatment significantly suppressed SGIV and RGNNV entry into host cells. The similar inhibitory effect on SGIV entry was observed in EcCH25H overexpression cells. Taken together, our findings demonstrated that EcCH25H inhibited SGIV and RGNNV infection by regulating IFN signaling molecules, and might also influence viral entry via an effect on cholesterol
Fish Autophagy Protein 5 Exerts Negative Regulation on Antiviral Immune Response Against Iridovirus and Nodavirus
Autophagy is an important biological activity that maintains homeostasis in eukaryotic cells. However, little is known about the functions of fish autophagy-related genes (Atgs). In this study, we cloned and characterized Atg5, a key gene in the autophagy gene superfamily, from orange-spotted grouper (Epinephelus coioides) (EcAtg5). EcAtg5 encoded a 275-amino acid protein that shared 94 and 81% identity to seabass (Lates calcarifer) and humans (Homo sapiens), respectively. The transcription level of EcAtg5 was significantly increased in cells infected with red-spotted grouper nervous necrosis virus (RGNNV). In cells infected with Singapore grouper iridovirus (SGIV), EcAtg5 expression declined during the early stage of infection and increased in the late stage. Fluorescence microscopy revealed that EcAtg5 mainly localized with a dot-like pattern in the cytoplasm of grouper cells. Overexpression of EcAtg5 significantly increased the replication of RGNNV and SGIV at different levels of detection, as indicated by increased severity of the cytopathic effect, transcription levels of viral genes, and levels of viral proteins. Knockdown of EcAtg5 decreased the replication of RGNNV and SGIV. Further studies showed that overexpression EcAtg5 activated autophagy, decreased expression levels of interferon related cytokines or effectors and pro-inflammatory factors, and inhibited the activation of nuclear factor κB, IFN-sensitive response element, and IFNs. In addition, ectopic expression of EcAtg5 affected cell cycle progression by hindering the G1/S transition. Taken together, our results demonstrated that fish Atg5 exerted a crucial role in virus replication by promoting autophagy, down-regulating antiviral IFN responses, and affecting the cell cycle
Pulse Diagnosis Signals Analysis of Fatty Liver Disease and Cirrhosis Patients by Using Machine Learning
Objective. To compare the signals of pulse diagnosis of fatty liver disease (FLD) patients and cirrhosis patients. Methods. After collecting the pulse waves of patients with fatty liver disease, cirrhosis patients, and healthy volunteers, we do pretreatment and parameters extracting based on harmonic fitting, modeling, and identification by unsupervised learning Principal Component Analysis (PCA) and supervised learning Least squares Regression (LS) and Least Absolute Shrinkage and Selection Operator (LASSO) with cross-validation step by step for analysis. Results. There is significant difference between the pulse diagnosis signals of healthy volunteers and patients with FLD and cirrhosis, and the result was confirmed by 3 analysis methods. The identification accuracy of the 1st principal component is about 75% without any classification formation by PCA, and supervised learning’s accuracy (LS and LASSO) was even more than 93% when 7 parameters were used and was 84% when only 2 parameters were used. Conclusion. The method we built in this study based on the combination of unsupervised learning PCA and supervised learning LS and LASSO might offer some confidence for the realization of computer-aided diagnosis by pulse diagnosis in TCM. In addition, this study might offer some important evidence for the science of pulse diagnosis in TCM clinical diagnosis
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