The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis

<div><p>Objective</p><p>In current clinical practice, optimal treatment of inflammatory bowel disease (IBD) aims at the induction and maintenance of clinical remission. Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to categorize patients with clinical remission into subsets with variable states of immune activation.</p><p>Design</p><p>By using Affymetrix GeneChips, we analysed RNA gene expression profiles of peripheral blood leukocytes from pediatric IBD patients in clinical remission and controls. We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients.</p><p>Results</p><p>Pediatric IBD patients with disease in clinical remission display heterogeneously distributed gene expression profiles that are significantly distinct from controls. We identified three clusters of IBD patients, each displaying specific expression profiles of IBD-associated genes.</p><p>Conclusion</p><p>The expression of immune- and IBD-associated genes in peripheral blood leukocytes from pediatric IBD patients in clinical remission was different from healthy controls, indicating that sub-clinical immune mechanisms are still active during remission. As such, RNA profiling of peripheral blood may allow for non-invasive patient subclassification and new perspectives in treatment regimes of IBD patients in the future.</p></div

Műszerügyi és Méréstechnikai Közlemények

UNIDO Workshop a Műszerügyi és Méréstechnikai Szolgálatnál Újszerű lehetőségek a Kutatófilm és Videotechnikai Főosztályon Műszerkölcsönzés Császár László: Üzemeltetési és szerviztapasztalataink (3.) A GOULD gyártmányú digitális oszcilloszkópok Új irányok a műszer- és méréstechnikában Radnai Rudolf: Gyakorlati tanácsok számítógépes mérőrendszerek üzembehelyezéséhez és üzemeltetéséhez Kőfalvi Jenő: Mikrovezetékes analitika az integrált áramkörök mintájára Szaktanácsadás Kőfalvi Jenő: Válogatás az Országos Műszernyilvántartás nagyértékű műszerújdonságaiból Külföldi műszerújdonságok. Összeállította: Csont Tamás - Fekete Gábor - Kőfalvi Jenő Könyvismertetés. Összeállította: Radnai Rudolf - Kőfalvi Jenő Műszerkölcsönzés Görgényi László: A kölcsönműszerpark szaporulata Szolgálatunk életébő

Molecular network generated by the Ingenuity software from the “Mouse High CPE expression sub-dataset”.

<p>Example of a molecular network generated by Ingenuity from the “Mouse High CPE expression sub-dataset (>90^th P)” of the microarray analysis. For explanation of symbols on the diagrams see legend <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083345#pone-0083345-g002" target="_blank">Figure 2</a>. The genes <i>PFKL</i>, <i>PFKM</i> and <i>PFKP</i> were previously implicated in glucose metabolism and <i>CA2</i>, <i>CA12</i> and <i>CA14</i> were attributed to diseases with disturbed lipid and/or glucose metabolism and are involved in CSF production. These genes are indicated bold in the Figure. The main functionalities given by Ingenuity for this entire molecular network are ‘Carbohydrate metabolism, ophthalmic disease and metabolic disease’.</p

Clathrin-mediated endocytosis signaling pathway identified by the Ingenuity software in the “Mouse High CPE expression sub-dataset”.

<p>This is one of the canonical pathways that contained statistically significantly more genes than expected by chance in the group of genes that are highly expressed in the mouse CPE. Gray fields indicate their presence in the “Mouse High CPE expression sub-dataset (>90^th P)”; uncolored genes are added by the Ingenuity software to show the entire standard pathway. Solid lines between molecules indicate direct physical relationships between molecules (such as regulating and interacting protein domains). Abbreviations of gene names are according to standard abbreviations used in GenBank. As shown, the majority of genes of this pathway are highly expressed in the mouse CPE.</p

Molecular network generated by the Ingenuity software from the “Mouse High CPE expression sub-dataset”.

<p>Example of a molecular network generated by Ingenuity from the “Mouse High CPE expression sub-dataset (>90^th P)” of the microarray analysis. For explanation of symbols on the diagrams see legend <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083345#pone-0083345-g002" target="_blank">Figure 2</a>. In this network there are genes involved in maturation of embryonic stem cells, generation of dopaminergic neurons and survival of RPE cells (<i>BCL2L1</i>), size of the eye (<i>AES, TLE1</i>), development of neural crest (<i>MSX1</i>), morphogenesis of cartilage tissue and middle ear (<i>MSX1</i>), and apoptosis of the embryoblast (<i>TAF10</i>). These genes are indicated bold in the Figure. The main functionalities given by Ingenuity for this entire molecular network are ‘Gene expression, embryonic and organ development’.</p

Comparison of different human and mouse CPE gene expression analysis.

<p>Comparison of our (bold printed) human and mouse CPE gene expressions, functional annotation and specifically expressed genes with those of previously published human and mouse CPE transcriptomes.</p><p>¹ Total numbers of genes in the High Expression (>90th percentile (P)) sub-datasets.</p><p>² Comparison of the genes in the >90th P of different datasets from literature with our “Human and Mouse High CPE expression (>90^th P) sub-datasets” per species. The number and percentage of overlap is given.</p><p>³ Comparison of the functional annotation (Funct. Annot); h-s = highly similar.</p><p>⁴ Comparison with mouse specific functions. Metab = Metabolism: metabolic function and diseases, including carbohydrate metabolism, lipid metabolism, aciduria, mitochondrial disorder, hyperglycemia, hypoglycemia and amyloidosis. Dev = Development: More extensive list of developmental functions, including development of eye, cornea, cortex, brain and embryo-size. Clath = Clathrin: Clathrin-mediated endocytosis signaling.</p><p>⁵ Comparison with specifically expressed genes. We identified three genes that we specifically expressed in mouse CPE compared to the human CPE, namely <i>ACE</i>, <i>PON1</i> and <i>TRIM3</i>. We subdivided the gene expression data of human and mouse CPE from literature also in groups based on percentiles (P): high (H) (>90^th P), moderate (M) (50–90^th P), low (L) (10–50^th P) and very low (VL) (<10^th P) and we looked in which of these groups the three genes were expressed in the gene expression databases from literature. Sometimes, no data were available for a gene (indicated with “x”).</p

Expression of epithelial junction genes in human and mouse CPE.

<p>This diagram illustrates the distribution of expression of epithelial junction genes in human and mouse CPE, subdivided in the four sub-datasets (very low (<10^th P); low (10–50^th P); moderate (50–90^th P); and high (>90^th P); see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083345#s2" target="_blank">Methods</a>). On the x-axis, the four different expression subgroups are displayed, on the y-axis the number of genes. The black solid lined circles contain epithelial junctions expressed in human CPE expression data and the grey dotted lined circles include those of the mouse CPE. The epithelial junction genes showed overlap in expression category between human and mouse CPE, and none of them showed a difference in expression more than one sub-dataset between human and mouse. For example, the genes CDH1 and CDH3 were highly expressed in human CPE and moderately in mouse CPE, whereas the genes CLDN2 and CLDN3 were highly expressed in mouse CPE and moderately in human CPE and the gene CTNNB1 was highly expressed in both human and mouse CPE.</p

Molecular network generated by the Ingenuity software from the “Human High CPE expression sub-dataset”.

<p>Example of a molecular network generated by Ingenuity from the “Human High CPE expression sub-dataset (>90^th P)” of the microarray analysis. For explanation of symbols on the diagrams see legend <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083345#pone-0083345-g002" target="_blank">Figure 2</a>. This network contains several genes that code for proteins involved in transport of specific biomolecules, namely <i>CYTB</i> and <i>UQCR11</i> (transport of H+), <i>MUT</i> and <i>NFE2L1</i> (transport of glutathione and carnitine), <i>VDAC3</i> (transport of adenine) and <i>C1QBP</i> (transport of hyaluronic acid and lactic acid). The genes mentioned are indicated bold in the Figure. The main functionalities given by Ingenuity for this entire molecular network are ‘Hereditary disorder, metabolic disease and molecular transport’.</p

CPE gene expression of ion channel proteins implicated in CSF production.

<p>Expression levels of genes coding for ion channel proteins implicated in cerebrospinal fluid (CSF) production in healthy human and mouse CPE. We ranked the genes by expression level and assigned percentile ranks (P). Next, we formed four groups: high (H) expression (expression >90th P), moderate (M) expression (50–90th P), low (L) expression (10–50th P) and very low (VL) expression (<10th P). This means that a gene in the high expression group (>90th P) has an expression intensity that falls into the highest 10% intensity values of the microarray, whereas a gene in the very low expression group (<10th P) has an expression intensity in the lowest 10% intensity values of the microarray. For genes indicated with “-”, no data were available.</p><p>Abbreviations: H1 = our gene expression data of healthy human CPE; M1 = our gene expression data of healthy mouse CPE; H2 = healthy human CPE GSE14098; M2 = healthy mouse CPE GSE23714; M3 = healthy mouse CPE GSE37098; M4 = healthy mouse CPE GSE33009.</p

A Revision of the Section of Chemung Rocks Exposed in the Gulf Brook Gorge at LeRoy, in Bradford County, Pennsylvania

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