Microglial transcription profiles in mouse and in human are driven by APOE4 and sex

AbstractNovel and sensitive biomarkers is highly required for early detection and predicting prognosis of hepatocellular carcinoma (HCC). Here, we investigated transcription profiles from peripheral blood mononuclear cells (PBMCs) of 8 patients with HCC and PBMCs from co-culture model with HCC using RNA-Sequencing. These transcription profiles were cross compared with published microarray datasets of PBMCs in HCC to identify differentially expressed genes (DEGs). A total of commonly identified of 24 DEGs among these data were proposed as cancer-induced genes in PBMCs, including 18 upregulated and 6 downregulated DEGs. The KEGG pathway showed that these enriched genes were mainly associated with immune responses. Five up-regulated candidate genes including BHLHE40, AREG, SOCS1, CCL5, and DDIT4 were selected and further validated in PBMCs of 100 patients with HBV-related HCC, 100 patients with chronic HBV infection and 100 healthy controls. Based on ROC analysis, BHLHE40 and DDIT4 displayed better diagnostic performance than alpha-fetoprotein (AFP) in discriminating HCC from controls. Additionally, BHLHE40 and DDIT4 had high sensitivity for detecting AFP-negative and early-stage HCC. BHLHE40 was also emerged as an independent prognostic factor of overall survival of HCC. Together, our study indicated that BHLHE40 in PBMCs could be a promising diagnostic and prognostic biomarker for HBV-related HCC.

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Tissue-specific transcription profiles of sex steroid biosynthesis enzymes and the androgen receptor

Journal of Molecular Medicine ◽

10.1007/s00109-006-0049-1 ◽

2006 ◽

Vol 84 (8) ◽

pp. 651-659 ◽

Cited By ~ 14

Author(s):

U. Hoppe ◽

P.-M. Holterhus ◽

L. Wünsch ◽

D. Jocham ◽

T. Drechsler ◽

...

Keyword(s):

Androgen Receptor ◽

Sex Steroid ◽

Steroid Biosynthesis ◽

Tissue Specific ◽

Transcription Profiles

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Sustained in vivo blockade of α1-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00100.2013 ◽

2013 ◽

Vol 305 (2) ◽

pp. E194-E204 ◽

Cited By ~ 12

Author(s):

Natasa J. Stojkov ◽

Marija M. Janjic ◽

Aleksandar Z. Baburski ◽

Aleksandar I. Mihajlovic ◽

Dragana M. Drljaca ◽

...

Keyword(s):

Adrenergic Receptors ◽

Leydig Cells ◽

High Affinity ◽

Testosterone Production ◽

Transcription Profiles ◽

Steroidogenic Cells ◽

Main Regulator ◽

Stimulatory Factor

This study was designed to systematically analyze and evaluate the effects of in vivo blockade of α1-adrenergic receptors (α1-ADRs) on the stress-induced disturbance of steroidogenic machinery in Leydig cells. Parameters followed 1) steroidogenic enzymes/proteins, transcription factors, and cAMP/testosterone production; 2) the main hallmarks of stress (epinephrine, glucocorticoids); and 3) transcription profiles of ADRs and oxidases with high affinity to inactivate glucocorticoids. Results showed that sustained blockade of α1-ADRs prevented stress-induced 1) decrease of the transcripts/proteins for main steroidogenic CYPs (CYP11A1, CYP17A1); 2) decrease of Scarb1 and Hsd3b1 transcripts; 3) decrease of transcript for Nur77, one of the main activator of the steroidogenic expression; and 4) increase of Dax1 and Arr19, the main steroidogenic repressors in Leydig cells. In the same cells, the expression of steroidogenic stimulatory factor Creb1, StAR, and androgen receptor increased. In this signaling scenario, stress-induced stimulation of Adra1a/Adra1b/Adrbk1 and Hsd11b2 (the unidirectional oxidase with high affinity to inactivate glucocorticoids) was not changed. Blockade additionally stimulated stress-increased transcription of the most abundantly expressed ADRs Adra1d/Adrb1/Adrb2 in Leydig cells. In the same cells, stress-decreased testosterone production, the main marker of Leydig cells functionality, was completely prevented, while reduction of cAMP, the main regulator of androgenesis, was partially prevented. Accordingly, the presented data provide a new molecular/transcriptional base for “fight/adaptation” of steroidogenic cells and new molecular insights into the role of α1-ADRs in stress-impaired Leydig cell steroidogenesis. The results are important in term of wide use of α1-ADR selective antagonists, alone/in combination, to treat high blood pressure, nightmares associated with posttraumatic stress disorder, and disrupted sexual health.

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Transcription Profiling ofCandida albicansCells Undergoing the Yeast-to-Hyphal Transition

Molecular Biology of the Cell ◽

10.1091/mbc.e02-05-0272 ◽

2002 ◽

Vol 13 (10) ◽

pp. 3452-3465 ◽

Cited By ~ 271

Author(s):

André Nantel ◽

Daniel Dignard ◽

Catherine Bachewich ◽

Doreen Harcus ◽

Anne Marcil ◽

...

Keyword(s):

Time Course ◽

Dna Microarrays ◽

Culture Medium ◽

Developmental Process ◽

Pathogenic Fungus ◽

Hyphal Growth ◽

Transcription Profiles ◽

Hyphal Morphology ◽

External Signals ◽

Temperature Time

The ability of the pathogenic fungus Candida albicans to switch from a yeast to a hyphal morphology in response to external signals is implicated in its pathogenicity. We used glass DNA microarrays to investigate the transcription profiles of 6333 predicted ORFs in cells undergoing this transition and their responses to changes in temperature and culture medium. We have identified several genes whose transcriptional profiles are similar to those of known virulence factors that are modulated by the switch to hyphal growth caused by addition of serum and a 37°C growth temperature. Time course analysis of this transition identified transcripts that are induced before germ tube initiation and shut off later in the developmental process. A strain deleted for the Efg1p and Cph1p transcription factors is defective in hyphae formation, and its response to serum and increased temperature is almost identical to the response of a wild-type strain grown at 37°C in the absence of serum. Thus Efg1p and Cph1p are needed for the activation of the transcriptional program that is induced by the presence of serum.

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Differential transcription profiles in Trypanosoma cruzi associated with clinical forms of Chagas disease: Maxicircle NADH dehydrogenase subunit 7 gene truncation in asymptomatic patient isolates

Molecular and Biochemical Parasitology ◽

10.1016/j.molbiopara.2006.08.008 ◽

2006 ◽

Vol 150 (2) ◽

pp. 236-248 ◽

Cited By ~ 19

Author(s):

Cassio S. Baptista ◽

Ricardo Z.N. Vêncio ◽

Sarah Abdala ◽

Julio César Carranza ◽

Scott J. Westenberger ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Nadh Dehydrogenase ◽

Asymptomatic Patient ◽

Nadh Dehydrogenase Subunit ◽

Clinical Forms ◽

Transcription Profiles ◽

Differential Transcription

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The Two-Component Regulatory System TCS08 Is Involved in Cellobiose Metabolism of Streptococcus pneumoniae R6

Journal of Bacteriology ◽

10.1128/jb.01170-06 ◽

2006 ◽

Vol 189 (4) ◽

pp. 1342-1350 ◽

Cited By ~ 46

Author(s):

Stuart J. McKessar ◽

Regine Hakenbeck

Keyword(s):

Streptococcus Pneumoniae ◽

Response Regulator ◽

Regulatory System ◽

Phosphotransferase System ◽

Two Component System ◽

Transcription Profiles ◽

Regulatory Systems ◽

Two Component ◽

Cognate Response Regulator ◽

Gram Positive Cocci

ABSTRACT The two-component system TCS08 is one of the regulatory systems that is important for virulence of Streptococcus pneumoniae. In order to investigate the TCS08 regulon, we have analyzed transcription profiles of mutants derived from S. pneumoniae R6 by microarray analysis. Since deletion mutants are often without a significant phenotype, we constructed a mutation in the histidine kinase HK08, T133P, in analogy to the phosphatase mutation T230P in the H box of the S. pneumoniae CiaH kinase described recently (D. Zähner, K. Kaminski, M. van der Linden, T. Mascher, M. Merai, and R. Hakenbeck, J. Mol. Microbiol. Biotechnol. 4:211-216, 2002). In addition, a deletion mutation was constructed in rr08, encoding the cognate response regulator. The most heavily suppressed genes in the hk08 mutant were spr0276 to spr0282, encoding a putative cellobiose phosphoenolpyruvate sugar phosphotransferase system (PTS). Whereas the R6 Smr parent strain and the Δrr08 mutant readily grew on cellobiose, the hk08 mutant and selected mutants with deletions in the PTS cluster did not, strongly suggesting that TCS08 is involved in the catabolism of cellobiose. Homologues of the TCS08 system were found in closely related streptococci and other gram-positive cocci. However, the genes spr0276 to spr0282, encoding the putative cellobiose PTS, represent a genomic island in S. pneumoniae and homologues were found in Streptococcus gordonii only, suggesting that this system might contribute to the pathogenicity potential of the pneumococcus.

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Transcription profiles of the bacterium Mycoplasma pneumoniae grown at different temperatures

Nucleic Acids Research ◽

10.1093/nar/gkg841 ◽

2003 ◽

Vol 31 (21) ◽

pp. 6306-6320 ◽

Cited By ~ 59

Author(s):

J. Weiner III

Keyword(s):

Mycoplasma Pneumoniae ◽

Transcription Profiles ◽

Different Temperatures

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The Redox Regulator Fnr Is Required for Fermentative Growth and Enterotoxin Synthesis in Bacillus cereus F4430/73

Journal of Bacteriology ◽

10.1128/jb.01701-06 ◽

2007 ◽

Vol 189 (7) ◽

pp. 2813-2824 ◽

Cited By ~ 46

Author(s):

Assia Zigha ◽

Eric Rosenfeld ◽

Philippe Schmitt ◽

Catherine Duport

Keyword(s):

Bacillus Cereus ◽

Anaerobic Fermentation ◽

Virulence Gene ◽

Two Component System ◽

Component System ◽

Transcription Profiles ◽

Catabolic Genes ◽

Two Component ◽

Regulatory Impact ◽

Fermentative Growth

ABSTRACT Glucose-grown cells of Bacillus cereus respond to anaerobiosis and low extracellular oxidoreduction potentials (ORP), notably by enhancing enterotoxin production. This response involves the ResDE two-component system. We searched the B. cereus genome for other redox response regulators potentially involved in this adaptive process, and we identified one gene encoding a protein predicted to have an amino acid sequence 58% identical (80% similar) to that of the Bacillus subtilis Fnr redox regulator. The fnr gene of the food-borne pathogen B. cereus F4430/73 has been cloned and partially characterized. We showed that fnr was up-regulated during anaerobic fermentation, especially when fermentation occurred at low ORP (under highly reducing conditions). The expression of fnr was down-regulated in the presence of O2 and nitrate which, unlike fumarate, stimulated the respiratory pathways. The inactivation of B. cereus fnr abolished fermentative growth but only moderately affected aerobic and anaerobic nitrate respiratory growth. Analyses of glucose by-products and the transcription profiles of key catabolic genes confirmed the strong regulatory impact of Fnr on B. cereus fermentative pathways. More importantly, the fnr mutation strongly decreased the expression of PlcR-dependent hbl and nhe genes, leading to the absence of hemolysin BL (Hbl) and nonhemolytic enterotoxin (Nhe) secretion by the mutant. These data indicate that fnr is essential for both fermentation and toxinogenesis. The results also suggest that both Fnr and the ResDE two-component system belong to a redox regulatory pathway that functions at least partially independently of the pleiotropic virulence gene regulator PlcR to regulate enterotoxin gene expression.

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