OVEREXPRESSION OF STAT4 - A POSSIBLE DIAGNOSTIC MARKER OF EARLY STAGES OF MYCOSIS FUNGOIDES

Background. Mycosis fungoides (MF) is the most common disease among the cutaneous T-cell lymphomas (85-90%). The accuracy of the diagnosis of MF, which is confirmed only by clinical, histological and immunohistochemical signs, is 50-75%. The aim of the study was to investigate genetic markers (FOXP3, STAT4, IL-12B) for early diagnosis of mycosis fungoides. Material and methods. A study involving 42 patients with MF and plaque parapsoriasis (PP) treated at the Dermatology Department of I.M. Sechenov First Moscow State Medical University and National Medical Hematology Research Сenter, was performed. The analysis of gene expression FOXP3, STAT4, IL-12B was carried out by TaqMan Real time-PCR. The objects of the study were lesional skin samples of patients. A group with MF consisted of 29 patients, a group with PP consisted of 13 patients, a control group included 10 healthy volunteers. Results. The study revealed that the level of STAT4 gene expression showed a significant (9 times) increase in the mRNA expression of STAT4 transcripts in patients with MF (166) compared with patients with PP (17.9; p < 0.05) and 553 times - with healthy volunteers (0.3; p < 0.05). There was also a statistically significant predominance of the level of mRNA expression of STAT4 transcripts in patients with spotted and plaque stages of MF (180; 318) compared with patients with PP (17.9; p < 0.05) and healthy volunteers (0.3; p < 0.05), as well as a sharp decrease in patients with erythrodermic form of MF (7.19). For early diagnosis of MF the level of expression of mRNA transcripts STAT4 is of great importance. Inclusion of STAT4 in the list of diagnostic features increases the accuracy of differential diagnosis of MF and PP from 59.1 to 81.8%.

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Optimization of the molecular genetics for the diagnosis of early mycosis fungoides

Russian Journal of Skin and Venereal Diseases ◽

10.17816/dv61237 ◽

2021 ◽

Vol 24 (1) ◽

pp. 35-44

Author(s):

Olga Yu. Olisova ◽

Ekaterina V. Grekova ◽

Ekaterina A. Alekseeva ◽

Dmitry V. Zaletaev

Keyword(s):

Gene Expression ◽

Early Diagnosis ◽

Healthy Volunteers ◽

Mycosis Fungoides ◽

Diagnostic Algorithm ◽

Control Group ◽

Common Disease ◽

Lesional Skin ◽

T Cell Lymphomas ◽

Skin Samples

BACKGROUND: Mycosis fungoides (MF) is the most common disease among the cutaneous T-cell lymphomas (8590%). The accuracy of the diagnosis of MF, which is confirmed only by clinical, histological and immunohistochemical signs, is 5075%. AIMS: To investigate genetic marker STAT4 for early diagnosis of mycosis fungoides. MATERIALS AND METHODS: A study involving 42 patients with MF and chronic benign dermatoses (CBD) was performed. The analysis of gene expression STAT4 was carried out by TaqMan Real time-PCR. The objects of the study were lesional skin samples of patients. A group with MF consisted of 29 patients, a group with CBD consisted of 13 patients, a control group included 10 healthy volunteers. RESULTS: The study revealed that the level of STAT4 gene expression showed a significant (9 times) increase in the expression of gene STAT4 in patients with MF (168.2) compared with patients with CBD (18.5; p 0.001) and 561 times with healthy volunteers (0.3; p 0.001). CONCLUSION: For early diagnosis of MF the level of expression STAT4 is of great importance. Inclusion of STAT4 in the list of diagnostic algorithm increases the accuracy of differential diagnosis of MF and CBD from 59.1 to 92.2%.

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Abstract 14356: Blood Tests That Improve the Accuracy of a Brugada Syndrome Diagnosis

Circulation ◽

10.1161/circ.132.suppl_3.14356 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Anyu Zhou ◽

Ning Jinag ◽

Marco Denegri ◽

An Xie ◽

Guangbin Shi ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Brugada Syndrome ◽

Roc Analysis ◽

White Blood Cells ◽

Control Group ◽

Mrna Levels ◽

Operating Characteristics ◽

Optimal Cutoff ◽

Scn5a Mutation

Objectives: To discover the role of altered gene expression regulation in Brugada Syndrome (BrS) and to find biomarkers for BrS diagnosis. Methods: Twenty-five control patients (Control), 25 BrS patients without SCN5A mutation (SCN5A(-)) and 20 BrS patients with SCN5A mutation (SCN5A(+)) were included in this study. Specified gene expression of white blood cells (WBC) were measured by RT-qPCR using TaqMan® Gene Expression assay. Results: MEF2C and MESP1 are the two major cardiac specific transcription factors expressed in WBC. The mRNA expression levels of SCN5A, MEF2C and HuR, one of mRNA stabilizers, were decreased in the SCN5A (+) group (P=0.047, 0.02, 0.000 vs. control group, respectively). The mRNA expression of MESP1 in WBCs was significantly lower in both SCN5A(-) (P=0.012 vs. control) and SCN5A(+) (P=0.000 vs. control) groups. There was no difference between the two BrS groups in MESP1 expression (P=0.215). The area under the Receiver Operating Characteristics (ROC) analysis curve for prediction of BrS using MESP1 levels was 0.775 (95% CI 0.668, 0.882, asymptotic Sig.=0.000). At the optimal cutoff, the corresponding maximum sensitivity and specificity were 0.62 (95% CI: 0.47, 0.76) and 0.88 (0.69, 0.97), respectively. The diagnostic odds ratio (DOR) of MESP1 for BrS diagnosis was 11.96 (95% CI: 5.79, 24.73). The assessment of the mRNA levels in blood SCN5A, MEF2C and HuR were useful for predicting BrS patients with an SCN5A mutation. The area under the ROC analysis curve for prediction of BrS with an SCN5A mutation using SCN5A, MEF2C and HuR mRNA levels in WBCs was 0.847 (95% CI 0.752, 0.942, asymptotic Sig.=0.000), 0.685 (95% CI 0.542, 0.828, asymptotic Sig.=0.016) and 0.777 (95% CI 0.652, 0.902, asymptotic Sig.=0.000), respectively. At the optimal cutoff, the DOR of SCN5A, MEF2C and HuR for SCN5A(+) BrS diagnosis was 17.5 (95% CI: 8.06, 37.86), 4.9 (95% CI: 2.61, 9.17) and 23.5 (95% CI: 9.39, 58.80), respectively. Conclusions: Our results suggest that assessment of circulating MESP1 may be used as a biomarker for BrS diagnosis while decreased SCN5A, MEF2C and HuR mRNA in WBCs is associated with BrS patients with an SCN5A mutation. Our results also suggest that decreased expression of SCN5A, MEF2C, MESP1, and HuR may be pathophysiologically related to BrS.

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P3486Experimental model for heart failure in rats: apelin-13/apj and bnp-45 gene expression analysis

European Heart Journal ◽

10.1093/eurheartj/ehz745.0354 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H R Helmi ◽

A P Sunjaya ◽

D Limanan ◽

A R Prijanti ◽

S W A Jusman ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Cardiac Hypertrophy ◽

Mrna Expression ◽

Rat Model ◽

Control Group ◽

P Value ◽

Sprague Dawley ◽

Hypoxia Exposure ◽

Systemic Hypoxia

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia

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Cytokine Gene Expression and IgA Production in the Spleen of Chickens Infected with Eimeria tenella

Indian Journal of Animal Research ◽

10.18805/ijar.b-1188 ◽

2020 ◽

Cited By ~ 1

Author(s):

Liushu Jia ◽

Bianhua Zhou ◽

Hongwei Wang ◽

Fan Yang ◽

Guoyong Wang ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Morphological Characteristics ◽

Eimeria Tenella ◽

Cytokine Gene Expression ◽

Control Group ◽

Expression Levels ◽

New Strategy ◽

Iga Production ◽

Mrna Expression Levels

To explore the effect of Eimeria tenella infection on the cytokines gene expression and IgA production in the spleen of chickens, the morphological characteristics of the spleen were observed through optical and transmission electron microscopy. The IgA production was determined through immunohistochemistry. The mRNA expression levels of splenic cytokines were detected through real-time PCR. Compared to the control group, along with the infection of E. tenella, the splenic lymphocytes exhibited irregular and cracked membranes, mitochondria swelled even vacuolization, the IgA expression in spleen tissue was decreased by 55.57% (p lessthan 0.01). Likewise, the mRNA expression levels of IL-2 and IL-1â decreased by 40% (plessthan 0.01) and 43% p lessthan 0.05), respectively. By contrast, the IL-6, IFN-g and IL-10 levels increased by 158% (p lessthan 0.01), 464% (p lessthan 0.05) and 379% p lessthan 0.01), respectively. These results indicated that the spleen implement an important function in the antagonism of E. tenella, which suggest a new strategy to control coccidiosis by improving the peripheral immunity of chickens.

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Microarray study of gene expression profiles in peripheral blood samples from lung cancer patients before and after erlotinib treatment

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e19072 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e19072-e19072

Author(s):

A. Irigoyen ◽

C. Olmedo ◽

J. Valdivia ◽

A. Comino ◽

C. Cano ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Growth Factor ◽

Healthy Volunteers ◽

Cancer Patients ◽

Peripheral Blood ◽

Expression Profiles ◽

Control Group ◽

Blood Samples ◽

Lung Cancer Patients

e19072 Background: The gene expression profile in peripheral blood samples from lung cancer patients is a potential predictor to treatment response. Methods: The study has been developed using 10 healthy volunteers as the control group and 10 lung cancer patients (stage IV). Written informed consent was obtained being the protocol approved by the local Clinical Research and Ethics Committee. Peripheral blood samples were obtained from lung cancer patients before (T0) and after treatment (T15d). RNA from peripheral blood samples was extracted and purified selecting 28S/18S ratios>1.5 to obtain cDNA and cRNA for hybridization of the 20,000 genes included in Human 20K CodeLink. An array from each participant was obtained in duplicate. For each array, 2 μg of cRNA was compared to 2 μg of healthy cRNA.. Significant genes were found using Significance Analysis of Microarrays which uses repeated permutations of the data. Results: The selected genes were expressed >3-fold with a false discovery rate =0.05. Before treatment (T0) when patients were compared to healthy volunteers there was an increase in the expression of: histone 1 H4c, transforming growth factor beta 2, endothelial cell growth factor 1 (platelet-derived), glucose-6-phosphatase catalytic 2, Relaxin 3 receptor 1, Insulin-like growth factor binding protein 2, RAS-like family 11 member B, and ELK4. After treatment (T15d), when each lung cancer patient's results were compared to their own before treatment results (T0), there was an increase in the expression of: Bcl2, myosin light polypeptide 4; interferon alpha-inducible protein 27; interferon gamma receptor 1; RASSF5, ARHGEF6, IGFBP5, tumor protein p53 inducible nuclear protein 1, peroxisome proliferative activated receptor gamma. Conclusions: The data presented identifies biologically relevant over-expressed genes in lung cancer. A validation of these results and the analysis of the genes that identify patients who will respond positively to erlotinib treatment is being carried out. No significant financial relationships to disclose.

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Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

BioMed Research International ◽

10.1155/2013/190382 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Norma Dominguez-Avila ◽

Gabriel Ruiz-Castañeda ◽

Javier González-Ramírez ◽

Nora Fernandez-Jaramillo ◽

Jorge Escoto ◽

...

Keyword(s):

Gene Expression ◽

Pulmonary Hypertension ◽

Mrna Expression ◽

Cardiac Failure ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Control Group ◽

Endothelin 1 ◽

Mrna Gene ◽

Mrna Gene Expression

Transforming growth factor beta (TGFβ) is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβfamily and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (), whereas levels in animals with cardiac failure were intermediate. Conversely, TGFβ2 and TGFβ3 gene expression in lungs were higher in healthy animals than in ascitic animals in both groups (). TGFβ1, TβRI, and TβRII mRNA gene expression among healthy, ascitic, and chickens with cardiac failure showed no differences (). BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds ().

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Alteration of connexins gene expression by silibinin during hepatic warm ischemia-reperfusion injury in the rat model

10.32592/ircmj.2021.23.4.250 ◽

2021 ◽

Keyword(s):

Gene Expression ◽

Reperfusion Injury ◽

Mrna Expression ◽

Normal Saline ◽

Connexin 43 ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Hepatic Tissue ◽

Control Group ◽

Hepatic Ischemia

Background: Ischemia-reperfusion injury (IRI) is an injurious phenomenon that is the primary determinant of liver dysfunction after surgery and transplantation. The present evidence demonstrated that connexin 43 (Cx43), Cx32, and Cx26 are the essential gap junction proteins involved in the liver IRI. This study aimed to characterize the beneficial effects of silibinin on Cx43, Cx32, and Cx26 gene expression during warm hepatic ischemia-reperfusion (IR). Materials and Methods: A total of 32 male Wistar rats weighing 250-300 g were randomly divided into four equal groups of eight animals in each group as follows: 1) control group (laparotomy+normal saline), 2) laparotomy+silibinin (30 mg/kg) (SILI), 3) liver IR procedure+normal saline (IR), and 4) liver IR procedure+silibinin (30 mg/kg) (IR+SILI). After 1 h of ischemia followed by 3 h of reperfusion, blood samples and tissue sections were gathered to assess the serum liver markers and evaluate the liver histological changes as well as gene expression, respectively. Results: The obtained data proved no considerable differences between control and SILI groups in all experiments. Furthermore, the gene expression of Cx26, Cx32, and Cx43 was significantly induced in the IR group, compared to the control group. Silibinin markedly reduced Cx26 and Cx32 mRNA expression, whereas increased Cx43 mRNA expression. Moreover, serum alanine aminotransferase and aspartate aminotransferase levels were markedly elevated in the IR group (P<0.001), compared to the control group. However, in the IR+SILI group, silibinin could significantly decline these elevations, compared to the IR group. In addition, silibinin diminished hepatic tissue damages during IR. Conclusion: Silibinin could attenuate liver injury through better cell-to-cell communication via lowering Cx32 and Cx26, as well as increasing Cx43 gene expression, respectively.

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myoMIR and gene expression in myofibrillar myopathy

10.5327/1516-3180.662 ◽

2021 ◽

Author(s):

Matheus Moreira Perez ◽

David Feder, Beatriz da Costa Aguiar Alves ◽

Fernando Luiz Affonso Fonseca ◽

Alzira Alves de Siqueira Carvalho

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Muscle Biopsy ◽

Diagnostic Value ◽

Included Study ◽

Control Group ◽

Protective Function ◽

Muscle Disorders ◽

Skeletal Tissue ◽

Student’S T

Background: Myofibrillar myopathies (MFM) represent a heterogeneous group of muscle disorders caused by mutations in different genes. It has been identified a group of microRNAs present in muscles named myoMIR. Objective: Evaluate the diagnostic value of these myoMIRs and mRNA expression in skeletal tissue from muscle biopsy of patients with MFM. Design and Setting: Muscle biopsies from 16 MFM patients with mutations in Desmin (DES), Myotilin (MYOT), ZASP, or Filamin C (FLNC) genes, and 18 donors (patients with minimal non- specific changes in muscle biopsy) were included. Study were conducted at FMABC. Methods: mRNA and myoMIR expression from both groups were assessed. The target myoMIRs were MIR1, MIR133a, MIR133b, MIR206, MIR208a, MIR208b, MIR486, and MIR499. Anova and Student’s t-test were performed. Results: Six patients presented mutations in DES, five in ZASP, three in FLNC, and two in MYOT. MIR133b (p=0.05), MIR499 (p=0.027), and mRNA expression was up-regulated in patients with MFM. MIR208a (p=0.042) was higher in the control group. We found an association between MIR133a and the presence of mutations in all genes studied (p=0.006). A relation between MIR486 and mutations in ZASP and DES (p=0.035) was also noted. Conclusions: • MIR208a seems to have a protective function in the muscle fiber; • Heterogeneity could be related to the concentration of gene expression in each patient; • Expression of myoMIRs influences several aspects in the muscle function through genes modulation which are important to myogenesis control;

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mRNA Expression of CYP2E1, CYP2A19, CYP1A2, HSD3B, SULT1A1 and SULT2A1 genes in surgically castrated, immunologically castrated, entire male and female pigs and correlation with androstenone, skatole, indole and Improvac-specific antibody levels

Czech Journal of Animal Science ◽

10.17221/159/2018-cjas ◽

2019 ◽

Vol 64 (No. 2) ◽

pp. 89-97

Author(s):

A. Kubešová ◽

K. Šťastný ◽

M. Faldyna ◽

Z. Sládek ◽

I. Steinhauserová ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Mrna Level ◽

Boar Taint ◽

Control Group ◽

Mrna Levels ◽

Large White ◽

Specific Antibodies ◽

Significant Difference ◽

Entire Male

This study aimed to obtain a comprehensive look at the influence of castration on mRNA expression of the genes CYP2E1, CYP1A2, CYP2A19, HSD3B, SULT2A1 and SULT1A1 and their correlation with boar taint compounds (androstenone, skatole and indole) and Improvac-specific antibodies in a Czech commercial hybrid (Large White × Landrace (sow) × Duroc (boar)). Pigs were divided into groups of entire male pigs (NC), pigs castrated surgically (SC), pigs immunologically castrated and slaughtered 8 weeks (IM8) or 15 weeks (IM15) after the second dose of Improvac, and gilts (GI). Hepatic mRNA expression, measured by quantitative real-time polymerase chain reaction, differed significantly between the control group (entire male pigs) and all groups of interest for CYP2E1, CYP1A2 and CYP2A19. The mRNA level of the HSD3B gene differed significantly between the control group and the IM8, IM15 and GI groups. SULT1A1 gene expression was significantly different between the control group and the SC, IM8 and GI. In the case of SULT2A1, a significant difference was observed only between the control group and IM8 pigs. For all genes and treatment groups described above, expression was increased relative to the control. Significant differences for Improvac-specific antibodies between IM8 and IM15 groups were observed, indicating decrease of antibodies over time. Moreover, negative correlations between androstenone and mRNA levels of CYP2A19, CYP2E1 and SULT1A1 suggest that gene expression is suppressed.

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LPA Gene Polymorphisms and Gene Expression Associated with Coronary Artery Disease

BioMed Research International ◽

10.1155/2017/4138376 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Zi-Kai Song ◽

Hong-Yan Cao ◽

Hai-Di Wu ◽

Li-Ting Zhou ◽

Ling Qin

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Gene Polymorphisms ◽

Control Group ◽

Case Group ◽

Chinese Han ◽

Expression Levels ◽

Artery Disease ◽

Cad Risk ◽

Mrna Expression Levels

The aim of our study was to investigate the influence of LPA gene polymorphisms for CAD risk and Lp(a) in a case-control study of Chinese Han population. In addition, we further analyzed the effect of LPA gene expression on plasma levels of Lp(a) and CAD risk. First, five SNPs (rs1367211, rs3127596, rs6415085, rs9347438, and rs9364559) in LPA gene were genotyped using the SEQUENOM Mass-ARRAY system in two groups. Second, we used quantitative real-time PCR to examine the mRNA expression levels of LPA gene in 92 cases and 32 controls. Results showed that the frequency of rs6415085-T allele was significantly higher in case group than that in control group (P<0.05). Haplotypes were not associated with CAD risk (P>0.05). And cases with the TT/TG genotype had significantly higher plasma Lp(a) levels compared with those that have the rs6415085 GG genotype (P<0.05). Additionally, the mRNA expression levels in case group are significantly higher than that in control group (P<0.05). Our study confirmed that rs6415085 was associated with CAD and increased plasma Lp(a) levels. And increased mRNA expression level of LPA gene may be a mechanism in development of CAD.

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