scholarly journals Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

2020 ◽  
Author(s):  
Huijia Zhao ◽  
Ling Li ◽  
Qi-fa Ye
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Peripheral Blood ◽  
Kegg Pathway ◽  
Peripheral Blood Lymphocytes ◽  
Protein Stabilization ◽  
Gene Set Enrichment Analysis ◽  
Rna Transport ◽  
Ppi Network ◽  
Humoral And Cellular Immunity

Abstract Background: Acute rejection (AR) is one of common and critical complications after kidney transplantation, which gives rise to an increasing of allograft loss and even death. However, the potential mechanisms of AR remain incompletely understood at present. This study aimed to reveal the underlying mechanisms and identify core biomarkers of AR.Methods: The AR gene expression profile GSE1563 involving 6 renal transplant patients undergoing AR and 9 patients with well-functioning transplant with no clinical evidence of rejection was selected to analyze the differentially expressed genes (DEGs) from purified RNA of peripheral blood lymphocytes. DAVID was used to carry out Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was built to display the interactions among these DEGs. To get further reliable significant genes and mechanisms, gene set enrichment analysis (GSEA) was applied to evaluate the hub gene analyzing via PPI network.Results: A total of 347 DEGs were captured, including 301 upregulated genes and 46 downregulated genes. Go and KEGG pathway analysis showed the DEGs were particularly enriched in immune response, inflammatory response to antigenic stimulus, RNA transport and protein stabilization. The PPI network indicated 3 modules were also mainly involved in immune response and RNA transport. 18 hub genes were selected in PPI network, among which there were 6 core genes evaluated by DAVID. By the way of GSEA, Oxidative stress was another potential mechanism besides immunity and ncRNA transport. Conclusion: Our analysis uncovered the immune response including humoral and cellular immunity, ncRNA transport as well as oxidative stress was the major mechanisms of AR associated respectively with MAPK8, CCL5, HMGB1, NCBP2, XPO1 and APP, which could be novel noninvasive biomarkers in peripheral blood for early diagnosis and could be helpful to the treatment of AR.

scholarly journals Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

2020 ◽  
Author(s):  
Huijia Zhao ◽  
Ling Li ◽  
Qifa Ye
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Peripheral Blood ◽  
Kegg Pathway ◽  
Peripheral Blood Lymphocytes ◽  
Protein Stabilization ◽  
Gene Set Enrichment Analysis ◽  
Rna Transport ◽  
Ppi Network ◽  
Humoral And Cellular Immunity

Abstract Background: Acute rejection (AR) is one of common and critical complications after kidney transplantation, which gives rise to an increasing of allograft loss and even death. However, the potential mechanisms of AR remain incompletely understood at present. This study aimed to reveal the underlying mechanisms and identify core biomarkers of AR.Methods: The AR gene expression profile GSE1563 involving 6 renal transplant patients undergoing AR and 9 patients with well-functioning transplant with no clinical evidence of rejection was selected to analyze the differentially expressed genes (DEGs) from purified RNA of peripheral blood lymphocytes. DAVID was used to carry out Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was built to display the interactions among these DEGs. To get further reliable significant genes and mechanisms, gene set enrichment analysis (GSEA) was applied to evaluate the hub gene analyzing via PPI network.Results: A total of 347 DEGs were captured, including 301 upregulated genes and 46 downregulated genes. Go and KEGG pathway analysis showed the DEGs were particularly enriched in immune response, inflammatory response to antigenic stimulus, RNA transport and protein stabilization. The PPI network indicated 3 modules were also mainly involved in immune response and RNA transport. 18 hub genes were selected in PPI network, among which there were 6 core genes evaluated by DAVID. By the way of GSEA, Oxidative stress was another potential mechanism besides immunity and ncRNA transport. Conclusion: Our analysis uncovered the immune response including humoral and cellular immunity, ncRNA transport as well as oxidative stress was the major mechanisms of AR associated respectively with MAPK8, CCL5, HMGB1, NCBP2, XPO1 and APP, which could be novel noninvasive biomarkers in peripheral blood for early diagnosis and could be helpful to the treatment of AR.

Semiautomated microfluorometric instrument and reagent system for monitoring disease-related immunosuppression.

1982 ◽  
Vol 28 (9) ◽  
pp. 1887-1893 ◽  
Author(s):  
D F Ranney ◽  
A J Quattrone
Keyword(s):  
Immune Response ◽  
Dna Content ◽  
Peripheral Blood ◽  
Fluorescence Enhancement ◽  
Photon Counting ◽  
Peripheral Blood Lymphocytes ◽  
Response Modulation ◽  
Blood Lymphocytes ◽  
Complex Test ◽  
Immune Response Modulation

Abstract Several common metabolites and drugs in the serum in of patients with inflammatory, infectious, autoimmune, immunodeficient, neoplastic, and toxicant-induced diseases can produce artifactual suppression of the [methyl-3H]-thymidine assay, which is widely used to evaluate lymphocyte responsiveness. We have developed a sensitive, semiautomated, fluorescence-enhancement assay in which true immunosuppressors are measured in the presence of absence of such interfering substances. Peripheral blood lymphocytes are activated with mitogens in standard microtiter culture trays. Changes in lymphocyte DNA content are quantified with a reagent formulation containing mithramycin, the fluorescence of which is enhanced on binding to DNA in the presence of MgCl2. We solubilize cells within the intact microtiter tray by using an automated, inverted "Array Sonicator," and measure fluorescence with an automated, photon-counting fluorometer. With this system, immune response modulation can be accurately assessed in the presence of patients' sera and other complex test substances (e.g., supernates from hybridomas, fermentation vats, viral preparations, and macrophage cultures.

Immune Response and Mitosis of Human Peripheral Blood Lymphocytes in vitro

Science ◽  
1963 ◽  
Vol 142 (3596) ◽  
pp. 1185-1187 ◽  
Author(s):  
K. Hirschhorn ◽  
F. Bach ◽  
R. L. Kolodny ◽  
I. L. Firschein ◽  
N. Hashem
Keyword(s):  
Immune Response ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes

scholarly journals In vitro cytogenotoxic evaluation of sertraline

2018 ◽  
Vol 11 (3) ◽  
pp. 181-188
Author(s):  
Erman Salih Istifli ◽  
Rima Çelik ◽  
Mehmet Tahir Hüsunet ◽  
Nesrin Çetinel ◽  
Osman Demirhan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peripheral Blood ◽  
Dna Cleavage ◽  
Serotonin Reuptake ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Stress Index ◽  
Healthy Human ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes

Abstract Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 µg/mL) of SRT for 24- or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24- or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=−0.979, p<0.01; r=−0.930, p<0.05, respectively) when it was present for the last 48 hr (48-h treatment) of the culture period. SRT neither demonstrated a cleavage activity on plasmid DNA nor conferred DNA protection against H2O2. The application of various concentrations of SRT significantly increased the TOS and oxidative stress index (OSI) in human peripheral blood lymphocytes for both the 24- and 48-h treatment periods. Morover, the increase in TOS was potent as the positive control MMC at both treatment times. However, SRT did not alter the TAS levels in either 24- or 48-h treatment periods when compared to control. In addition, exposing cells to SRT caused significant decreases in the nuclear division index at 1.25, 2.50 and 3.75 µg/mL in the 24-h and at the highest concentration (5 µg/mL) in the 48-h treatment periods. Our results suggest that SRT may have cytotoxic effect via oxidative stress on cultured human peripheral blood lymphocytes.

Oxidative stress and thiol depletion in plasma and peripheral blood lymphocytes from HIV-infected patients

AIDS ◽  
1997 ◽  
Vol 11 (14) ◽  
pp. 1689-1697 ◽  
Author(s):  
Sharon L. Walmsley ◽  
Louise M. Winn ◽  
Maureen L. Harrison ◽  
Jack P. Uetrecht ◽  
Peter G. Wells
Keyword(s):  
Oxidative Stress ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes
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