WT-1 Expression Level In BM Is The Great Prognostic Marker In Three Of Classification IPSS, WPSS, and Latest Revised IPSS(IPSS-R)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2795-2795
Author(s):  
Sumiko Kobayashi ◽  
Yasunori Ueda ◽  
Mineo Kurokawa ◽  
Kiyoyuki Ogata ◽  
Hirohiko Shibayama ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Mrna Expression ◽  
Survival Time ◽  
Research Funding ◽  
Mrna Level ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Expression Levels ◽  
Wbc Count ◽  
Mrna Expression Levels

Abstract Objective/material/method It is known new classification named revised IPSS(IPSS-R) as a prognosis in MDS patients in 2012. To investigate the clinical utility of WT1 mRNA expression level including IPSS-R, we studied of MDS patients who provided consent at 17 medical institutions nationwide from Dec. 2008 to Sep. 2009 were enrolled in Japan. A total of 172 subjects including 115 MDS patients by IPSS (RA:69, RARS:9, RAEB:24, RAEB-t :13 ). 13 patients who developed AML from MDS, and 44 patients with non malignant hematological disorders who provided consent. This study was designed to follow up 82 patients, who gave secondary consent, among 115 MDS patients registered in study ODK-0801 for 5 years up to 2014 to analyze in detail the relationship between the WT1 mRNA expression level and prognosis. WT1 mRNA level in PB and BM were measured using the WT1 mRNA assay kit “OTSUKA” (OTSUKA PHARMACEUTICAL CO., LTD). WT1 mRNA expression levels in peripheral blood (and in bone marrow, if possible) were measured periodically to evaluate the usefulness of the WT1 mRNA expression level as a monitoring marker of MDS and analyze changes in pathology in individual patients by central review and changes in WT1 mRNA expression levels. In this study, value of 50 copies/μgRNA was set as the cut off value for WT-1mRNA expression. The differences in clinical and demographic data were assessed in the chi-square test and logistic regression analysis. The survival data was analyzed using Kaplan-Meier method and compared by the log-rank test. This study presents the results of interim analysis 3 years after the start of the investigation. Results The comparison study between the patients categorized into three groups by the WT1 mRNA level　in BM ,GroupI:less than 102 copies/μgRNA(n=35), Group II: 102 to 104 copies/μgRNA(n=30), and GroupIII: more than 104 copies/μgRNA(n=17) resulted that the survival rates decreased significantly as the WT1 mRNA level increased(GI vs GII P<0.01, GI vs GIII P<0.01, GII vs GIII p<0.067), respectively. In multivariate Cox proportional hazard regression analysis of IPSS, five out of fifteen parameters, which are WBC count (P=0.0001), IPSS score (P=0.0003), blast in PB(P=0.0011), WT1 mRNA level in BM(P=0.0055), sex(P=0.093) were independently associated with survival time, respectively. And we studied same analysis used WPSS. WBC count (P=0.0001), WPSS socre(P=0.0001), blast in PB(P=0.0037), WT1 mRNA level in BM(P=0.0029), sex(P=0.012) were independently associated with survival time, respectively. Also we analyzed using IPSS-R. In multivariate Cox proportional hazard regression analysis, five out of fifteen parameters, WBC count (P=0.0001), IPSS-R score(P=0.0001), blast in PB(P=0.0012), WT1 mRNA level in BM(P=0.01), sex(P=0.01) were independently associated with survival time, but not ANC(both score and absolute number), Hb, platelet, karyotype or other parameters. Using these selected five valiables, we provided the level of WT-1mRNA with 4 risk groups which classified :100, 50100, 100,100, 150,100copies/μRNA). According to increasing of WT-1mRNA level, survival duration shortened the increase with the increase in each risk group. Discussion The WT-1 mRNA level in BM was positively correlated with the prognosis of MDS stage and tended to be correlated with advanced risk of IPSS, WPSS, and IPSS-R. Therefore it was considered to be a useful prognostic marker for MDS. Conclusion We found that the survival time was shortened significantly with an increase in WT1 mRNA expression levels in both peripheral blood and bone marrow, demonstrating that WT1 mRNA expression levels are a highly useful prognostic factor in MDS even if we use any of classification of IPSS, WPSS, IPSS-R. This assay has great possibility to contribute to more appropriate therapeutic decisions in MDS patients as well as diagnosis and to evaluate the timing of allogeneic transplantation. Disclosures: Kurokawa: Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Research Funding. Usuki:Alexion Pharmaceuticals, Inc.: Speakers Bureau. Ohyashiki:Novartis: Honoraria, Research Funding.

scholarly journals Th2 cytokine bias induced by silver nanoparticles in peripheral blood mononuclear cells of common bottlenose dolphins (Tursiops truncatus)

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5432 ◽  
Author(s):  
Wen-Ta Li ◽  
Lei-Ya Wang ◽  
Hui-Wen Chang ◽  
Wei-Cheng Yang ◽  
Chieh Lo ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Bottlenose Dolphins ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Expression Levels ◽  
Th2 Cytokine ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mrna Expression Levels

Background Silver nanoparticles (AgNPs) have been widely used in many commercial products due to their excellent antibacterial ability. The AgNPs are released into the environment, gradually accumulate in the ocean, and may affect animals at high trophic levels, such as cetaceans and humans, via the food chain. Hence, the negative health impacts caused by AgNPs in cetaceans are of concern. Cytokines play a major role in the modulation of immune system and can be classified into two types: Th1 and Th2. Th1/Th2 balance can be evaluated by the ratios of their polarizing cytokines (i.e., interferon [IFN]-γ/Interleukin [IL]-4), and animals with imbalanced Th1/Th2 response may become more susceptible to certain kinds of infection. Therefore, the present study evaluated the in vitro cytokine responses of cetacean peripheral blood mononuclear cells (cPBMCs) to 20 nm citrate-AgNPs (C-AgNP20) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Methods Blood samples were collected from six captive common bottlenose dolphins (Tursiops truncatus). The cPBMCs were isolated and utilized for evaluating the in vitro cytokine responses. The cytokines evaluated included IL-2, IL-4, IL-10, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. The geometric means of two housekeeping genes (HKGs), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β2-microglobulin (B2M), of each sample were determined and used to normalize the mRNA expression levels of target genes. Results The ratio of late apoptotic/necrotic cells of cPBMCs significantly increased with or without concanavalin A (ConA) stimulation after 24 h of 10 µg/ml C-AgNP20 treatment. At 4 h of culture, the mRNA expression level of IL-10 was significantly decreased with 1 µg/ml C-AgNP20 treatment. At 24 h of culture with 1 µg/ml C-AgNP20, the mRNA expression levels of all cytokines were significantly decreased, with the exceptions of IL-4 and IL-10. The IFN-γ/IL-4 ratio was significantly decreased at 24 h of culture with 1 µg/ml C-AgNP20 treatment, and the IL-12/IL-4 ratio was significantly decreased at 4 or 24 h of culture with 0.1 or 1 µg/ml C-AgNP20 treatment, respectively. Furthermore, the mRNA expression level of TNF-α was significantly decreased by 1 µg/ml C-AgNP20 after 24 h of culture. Discussion The present study demonstrated that the sublethal dose of C-AgNP20 (≤1 µg/ml) had an inhibitory effect on the cytokine mRNA expression levels of cPBMCs with the evidence of Th2 cytokine bias and significantly decreased the mRNA expression level of TNF-α. Th2 cytokine bias is associated with enhanced immunity against parasites but decreased immunity to intracellular microorganisms. TNF-α is a contributing factor for the inflammatory response against the infection of intracellular pathogens. In summary, our data indicate that C-AgNP20 suppresses the cellular immune response and thereby increases the susceptibility of cetaceans to infection by intracellular microorganisms.

scholarly journals Th2 cytokine bias induced by silver nanoparticles in peripheral blood mononuclear cells of common bottlenose dolphins (Tursiops truncatus)

2018 ◽  
Author(s):  
Wen-Ta Li ◽  
Lei-Ya Wang ◽  
Hui-Wen Chang ◽  
Wei-Cheng Yang ◽  
Chieh Lo ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Bottlenose Dolphins ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Expression Levels ◽  
Th2 Cytokine ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mrna Expression Levels

Background Silver nanoparticles (AgNPs) have been widely used in many commercial products due to their excellent antibacterial ability. The AgNPs are released into the environment, gradually accumulate in the ocean, and may affect animals at high trophic level, such as cetaceans and humans, via the food chain. Hence, the negative health impacts caused by AgNPs in cetaceans are of concern. Cytokines play a major role in the modulation of immune system and can be classified into two types, Th1 and Th2. Th1/Th2 balance can be evaluated by the ratios of their polarizing cytokines (i.e., interferon [IFN]-γ/ Interleukin [IL]-4), and animals with imbalanced Th1/Th2 response may become more susceptible to certain kinds of infection. Therefore, the present study evaluated the in vitro cytokine responses of cetacean peripheral blood mononuclear cells (cPBMCs) to 20 nm citrate-AgNPs (C-AgNP20) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Methods Blood samples were collected from 6 captive common bottlenose dolphins (Tursiops truncatus). The cPBMCs were isolated and utilized for evaluating the in vitro cytokine responses. The cytokines evaluated included IL-2, IL-4, IL-10, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-ɑ. The geometric means of two housekeeping genes (HKGs), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β2-microglobulin (B2M), of each sample were determined and used to normalize the mRNA expression levels of target genes. Results The ratio of late apoptotic/necrotic cells of cPBMCs significantly increased with or without concanavalin A (ConA) stimulation after 24 h of 10 μg/ml C-AgNP20 treatment. At 4 h of culture, the mRNA expression level of IL-10 was significantly decreased with 1 μg/ml C-AgNP20 treatment. At 24 h of culture with 1 μg/ml C-AgNP20, the mRNA expression levels of all cytokines were significantly decreased, with the exceptions of IL-4 and IL-10. The IFN-γ/IL-4 ratio was significantly decreased at 24 h of culture with 1 μg/ml C-AgNP20 treatment, and the IL-12/IL-4 ratio was significantly decreased at 4 or 24 h of culture with 0.1 or 1 μg/ml C-AgNP20 treatment, respectively. Furthermore, the mRNA expression level of TNF-α was significantly decreased by 1 μg/ml C-AgNP20 after 24 h of culture. Discussion The present study demonstrated that the sublethal dose of C-AgNP20 (≤ 1 μg/ml) had an inhibitory effect on the cytokine mRNA expression levels of cPBMCs with the evidence of Th2 cytokine bias and significantly decreased the mRNA expression level of TNF-α. Th2 cytokine bias is associated with enhanced immunity against parasites but decreased immunity to intracellular microorganisms. TNF-α is a contributing factor for the inflammatory response against the infection of intracellular pathogens. In summary, our data indicate that C-AgNP20 suppresses the cellular immune response and thereby increases the susceptibility of cetaceans to infection by intracellular microorganisms.

scholarly journals Th2 cytokine bias induced by silver nanoparticles in peripheral blood mononuclear cells of common bottlenose dolphins (Tursiops truncatus)

2018 ◽  
Author(s):  
Wen-Ta Li ◽  
Lei-Ya Wang ◽  
Hui-Wen Chang ◽  
Wei-Cheng Yang ◽  
Chieh Lo ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Bottlenose Dolphins ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Expression Levels ◽  
Th2 Cytokine ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mrna Expression Levels

Background Silver nanoparticles (AgNPs) have been widely used in many commercial products due to their excellent antibacterial ability. The AgNPs are released into the environment, gradually accumulate in the ocean, and may affect animals at high trophic level, such as cetaceans and humans, via the food chain. Hence, the negative health impacts caused by AgNPs in cetaceans are of concern. Cytokines play a major role in the modulation of immune system and can be classified into two types, Th1 and Th2. Th1/Th2 balance can be evaluated by the ratios of their polarizing cytokines (i.e., interferon [IFN]-γ/ Interleukin [IL]-4), and animals with imbalanced Th1/Th2 response may become more susceptible to certain kinds of infection. Therefore, the present study evaluated the in vitro cytokine responses of cetacean peripheral blood mononuclear cells (cPBMCs) to 20 nm citrate-AgNPs (C-AgNP20) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Methods Blood samples were collected from 6 captive common bottlenose dolphins (Tursiops truncatus). The cPBMCs were isolated and utilized for evaluating the in vitro cytokine responses. The cytokines evaluated included IL-2, IL-4, IL-10, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-ɑ. The geometric means of two housekeeping genes (HKGs), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β2-microglobulin (B2M), of each sample were determined and used to normalize the mRNA expression levels of target genes. Results The ratio of late apoptotic/necrotic cells of cPBMCs significantly increased with or without concanavalin A (ConA) stimulation after 24 h of 10 μg/ml C-AgNP20 treatment. At 4 h of culture, the mRNA expression level of IL-10 was significantly decreased with 1 μg/ml C-AgNP20 treatment. At 24 h of culture with 1 μg/ml C-AgNP20, the mRNA expression levels of all cytokines were significantly decreased, with the exceptions of IL-4 and IL-10. The IFN-γ/IL-4 ratio was significantly decreased at 24 h of culture with 1 μg/ml C-AgNP20 treatment, and the IL-12/IL-4 ratio was significantly decreased at 4 or 24 h of culture with 0.1 or 1 μg/ml C-AgNP20 treatment, respectively. Furthermore, the mRNA expression level of TNF-α was significantly decreased by 1 μg/ml C-AgNP20 after 24 h of culture. Discussion The present study demonstrated that the sublethal dose of C-AgNP20 (≤ 1 μg/ml) had an inhibitory effect on the cytokine mRNA expression levels of cPBMCs with the evidence of Th2 cytokine bias and significantly decreased the mRNA expression level of TNF-α. Th2 cytokine bias is associated with enhanced immunity against parasites but decreased immunity to intracellular microorganisms. TNF-α is a contributing factor for the inflammatory response against the infection of intracellular pathogens. In summary, our data indicate that C-AgNP20 suppresses the cellular immune response and thereby increases the susceptibility of cetaceans to infection by intracellular microorganisms.

scholarly journals Cytokine and Chemokine mRNA Expressions after Mycobacterium tuberculosis-Specific Antigen Stimulation in Whole Blood from Hemodialysis Patients with Latent Tuberculosis Infection

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 595
Author(s):  
Ji Young Park ◽  
Sung-Bae Park ◽  
Heechul Park ◽  
Jungho Kim ◽  
Ye Na Kim ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mrna Expression ◽  
Whole Blood ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Healthy Individuals ◽  
Relative Mrna Expression ◽  
Mrna Expression Levels

There have been few reports on the kinetics of hemodialyzed (HD) patients’ immune responses in latent tuberculosis infection (LTBI). Therefore, in the present study, messenger ribonucleic acid (mRNA) expression levels of nine immune markers were analyzed to discriminate between HD patients with LTBI and healthy individuals. Nine cytokines and chemokines were screened through relative mRNA expression levels in whole blood samples after stimulation with Mycobacterium tuberculosis (MTB)-specific antigens from HD patients with LTBI (HD/LTBI), HD patients without LTBI, and healthy individuals, and results were compared with the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. We confirmed that the C-C motif chemokine 11 (CCL11) mRNA expression level of the HD/LTBI group was significantly higher than the other two groups. Especially, the CCL11 mRNA expression level of the >0.7 IU/mL group in the QFT-GIT test was significantly higher than the <0.2 IU/mL group in the QFT-GIT test and the 0.2–0.7 IU/mL group in the QFT-GIT test (p = 0.0043). The present study reveals that the relative mRNA expression of CCL11 was statistically different in LTBI based on the current cut-off value (i.e., ≥0.35 IU/mL) and in the >0.7 IU/mL group. These results suggest that CCL11 mRNA expression might be an alternative biomarker for LTBI diagnosis in HD patients.

scholarly journals Angiogenesis system, as a part of endothelial dysfunction in patients with diabetes mellitus type 2: relationship with obesity

2020 ◽  
Vol 92 (10) ◽  
pp. 23-28
Author(s):  
A. S. Severina ◽  
M. V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Mrna Expression ◽  
Body Mass ◽  
Diabetes Mellitus Type 2 ◽  
Diabetes Mellitus Type ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Patients With Diabetes ◽  
Mrna Expression Levels

Aim.To investigate parameters of angiogenesis system in patients with diabetes mellitus and their relationship with obesity. Materials and methods.104 patients with diabetes mellitus type 2 were included in the study. Patients were divided in 2 groups: Obesity+ (body mass index30 kg/m2;n=63) and Obesity- (body mass index 30 kg/m2;n=41). In all patients was performed clinico-diagnostical examination. mRNA expression levels of vascular endothelial growth factor (VEGF), its receptors flt-1 (fms-like tyrosine kinase 1), KDR (human kinase insert domain receptor) were determined in blood mononuclear cells. Results.There were no statistically significant differences in investigated parameters between study groups. mRNA expression level of VEGF was slightly lower in men compared to women: 0.19 (0.14; 0.32)vs0.28 (0.12; 0.4) respectively,р=0.2236. MRNA expression level of flt-1 was lower in men compared to women: 0.14 (0.04; 0.3)vs0.25 (0.12; 0.38),р=0.0321 (statistically significant). We found statistically significant correlations of mRNA expression level of VEGF with mRNA expression level of flt-1 and KDR. Also we found strong positive correlations of BMI and mRNA expression levels VEGF, flt-1, KDR (r=0.86107,r=0.86125,r=0.86112, respectively,p0.001). Conclusion.Results of the study displayed relationship of obesity and angiogenesis system condition in patients with diabetes mellitus type 2. Further investigations are perspective for the future as a way to new therapeutical approach of obesity and its complications treatment.

scholarly journals Expression and prognostic significance of MT1 isoforms in clear cell renal cell carcinoma

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 280
Author(s):  
Xiaohua Niu ◽  
Ling Deng ◽  
Chaoming Tang ◽  
Dexiang Zhuo
Keyword(s):  
Mrna Expression ◽  
Survival Time ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Tumor Biology ◽  
Prognostic Significance ◽  
High Expression ◽  
Expression Levels ◽  
Mrna Expression Levels

Metallothioneins (MTs), a family of low-weight cysteine-rich proteins, play key roles in tumor biology, such as proliferation, differentiation, apoptosis, and drug resistance. Clinical studies have demonstrated that deregulation of MTs in various types of solid cancers. However, a comprehensive overview of MT1 isoforms expression and clinical relevance in clear cell renal cell cancer (ccRCC) is lacking. The present study explored mRNA expression levels and prognostic values of MT1 isoforms in ccRCC tissues using The Cancer Genome Atlas (TCGA), Gene Expression Profiling and Interactive Analysis (GEPIA) and Oncomine database. The study observed that mRNA expression levels of six members of MT1 isoforms decreased in renal cancer tumor tissues compared with normal tissues. We further found that high-expression of MT1G, MT1H, MT1F and MT1X was related with poor overall survival time in ccRCC patients and high-expression of MT1G, MT1F and MT1X were inversely associated with disease-free survival time in ccRCC patients. Based on the correlation analysis, MT1G was identified to be co-expressed with MT1H and MT1F in ccRCC tissues. These findings suggested that MT1 isoforms mRNA may serve as diagnostic and prognostic markers for ccRCC.

scholarly journals Expression of genes modulated by epigallocatechin-3-gallate in breast cancer cells

2018 ◽  
Vol 64 (3) ◽  
pp. 31-37
Author(s):  
Anna Bogacz ◽  
Marlena Wolek ◽  
Bogna Juskowiak ◽  
Monika Karasiewicz ◽  
Adam Kamiński ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Expression Level ◽  
Mrna Levels ◽  
Mrna Expression Level

Summary Introduction: Breast cancer is the most common malignant cancer among women. Both drug resistance and metastasis are major problems in the treatment of breast cancer. Therefore, adjuvant therapy may improve patients’ survival and affect their quality of life. It is suggested that epigallocatechin gallate (EGCG) which is well known for its chemopreventive activity and acts on numerous molecular targets may inhibit the growth and metastasis of some cancers. Hence, discovering the metastatic molecular mechanisms for breast cancer may be useful for therapy. Objective: The aim of the study was to determine the effect of EGGC on the mRNA expression level of genes such as ZEB1, ABCB1, MDM2, TWIST1 and PTEN in MCF-7 breast cancer cells. Methods: MCF7/DOX were cultured in the presence of 0.2 μM DOX and EGCG (20-50 μM). The mRNA expression level was determined by real-time quantitative PCR using RealTime ready Custom Panel 96 kit. Results: Our results showed an important increase (about 2-fold for 20 μM EGCG + 0.2 μM DOX and 2.5-fold for 50 μM EGCG + 0.2 μM DOX, p<0.05) in ZEB1 expression levels. In case of ABCB1 gene lack of influence on the mRNA level was observed (p>0.05). We also observed significant decrease of ZEB1 expression in MCF7 cells with 20 μM and 50 μM EGCG (p<0.05). In addition, EGCG (20 μM) caused an increase of MDM2 and PTEN mRNA levels in almost 100% (p<0.05) and 40% (p>0.05), respectively. Lack of the influence of EGCG was noted for the TWIST1 gene expression. In case of MCF7/DOX we showed an increase of mRNA level of PTEN gene about 50% (p<0.05). Conclusions: These results suggest that EGCG may be potentially used in adjuvant therapy in the breast cancer treatment.

scholarly journals CD14, CD163, and CCR1 are involved in heart and blood communication in ischemic cardiac diseases

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095164
Author(s):  
Chengcong Chen ◽  
Hong Peng ◽  
Yongmei Zeng ◽  
Guoqing Dong
Keyword(s):  
Mrna Expression ◽  
Clinical Symptoms ◽  
Heart Diseases ◽  
Mrna Level ◽  
Functional Enrichment ◽  
Expression Level ◽  
Cardiac Diseases ◽  
Mrna Expression Level ◽  
Limma Package ◽  
Improve Patient Management

Objective Cardiac diseases lead to heart failure (HF), but the progression can take several years. Using blood samples to monitor changes in the heart before clinical symptoms begin may help to improve patient management. Methods Microarray data GSE42955 and GSE9128 were used as study datasets and GSE16499, GSE57338, and GSE59867 were used as validation groups. The “limma” package from R Language was used to identify differentially expressed genes. Functional enrichment analyses of gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were performed using Database for Annotation, Visualization and Integrated Discovery. We also investigated the correlation between the heart and blood using the mRNA expression level. Results Three hub genes, CD14, CD163, and CCR1, were identified. Functional enrichment analyses showed their involvement in the immune response and in the inflammatory response, which are the critical biochemical processes in ischemic HF. The mRNA expression level further demonstrated that a special model may exist to help to predict the mRNA level in the heart based on that in blood. Conclusions Our study identified three biomarkers that can connect the heart and blood in ischemic heart diseases, which may be a new approach to help better manage ischemic cardiac disease patients.

mRNA Expression Profile of SFKs and Involvement of SFKs in the Regulation of LPS-Induced Erk1/2 Signaling in PBMCs of Active BD Patients

2019 ◽  
Vol 19 (6) ◽  
pp. 809-817
Author(s):  
Sevgi Irtegun-Kandemir ◽  
Irmak Icen-Taskin ◽  
Mehtap Bozkurt ◽  
Sevgi Kalkanli-Tas
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Gradient Centrifugation ◽  
Mrna Level ◽  
Inflammatory Disorder ◽  
Protein Activity ◽  
Total Blood ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Mrna Expression Levels

Background: Behcet’s Disease (BD) is a multisystemic inflammatory disorder affecting large vessels, lungs joints, gastrointestinal and neurological systems. The pathogenesis of BD remains poorly understood. Identifying the key signaling pathway is crucial for a complete understanding of the pathogenesis of BD. Objective: The aim of this study was to determine mRNA expression level of Src family kinases (SFKs) members and their involvement in lipopolysaccharide (LPS)-induced mitogen-activated protein kinases (MAPKs) regulation in peripheral blood mononuclear cells (PBMCs) of active BD patients. Methods: Twenty- five active BD patients and twenty-five healthy controls were included in the study. PBMCs were isolated from total blood by density gradient centrifugation. The mRNA expression levels of SFKs members were measured by real-time quantitative PCR (RT-qPCR). The effect of SFKs activity on LPS-induced activation MAPKs (Erk1/2, p38 and JNK) was examined by Western blot. Results: The mRNA expression levels of Hck, Src, Lyn, Yes and Fyn were found to be slightly decreased in active BD patients compared to the control subjects, but a slight change in mRNA level of SFKs members did not impact on protein levels and protein activity. LPS-induced Erk1/2 phosphorylation was significantly increased in the absence of SFKs activity in active BD patients. However, inhibition of SFKs activity had no effect on LPS-induced phosphorylation of p38 and JNK in both controls and active BD patients. Conclusion: SFKs downregulate LPS-induced Erk1/2 phosphorylation in PBMCs of active BD patients.

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