Gene Expression Profile of Human Cytokines in Response to Burkholderia pseudomallei Infection

ABSTRACT Melioidosis is a life-threatening infectious disease caused by a soil-associated Gram-negative bacterium, B. pseudomallei. Melioidosis is endemic in Southeast Asia and northern Australia; however, the global distribution of B. pseudomallei and the disease burden of melioidosisis are still poorly understood. Melioidosis is difficult to treat, as B. pseudomallei is intrinsically resistant to many antibiotics and requires a long course of antibiotic treatment. The mortality rates remain high in areas of endemicity, with reoccurrence being common. Therefore, it is imperative to diagnose the disease at an early stage and provide vital clinical care to reduce the mortality rate. With limitations in treatment and lack of a vaccine, it is crucial to study the immune response mechanisms to this infection to get a better understanding of disease susceptibility and pathogenesis. Therefore, this study aimed to analyze the gene expression levels of important cytokines to establish useful correlations for diagnostic and therapeutic purposes. Melioidosis is an underreported infectious disease, caused by the Gram-negative bacterium Burkholderia pseudomallei. Understanding the disease susceptibility and pathogenesis is crucial for developing newer diagnostic and therapeutic strategies for this life-threatening infection. In this study, we aimed to analyze the gene expression levels of important cytokines in melioidosis patients and establish useful correlates with disease biomarkers compared to cases of sepsis infection caused by other pathogens and healthy individuals. A Qiagen common human cytokines array profiling the gene expression of 84 important cytokines by real-time quantitative PCR (RT-qPCR) was used. We analyzed 26 melioidosis cases, 5 healthy controls, and 10 cases of sepsis infection caused by other pathogens. Our results showed consistently upregulated expression of interleukins (IL) interleukin-4 (IL-4), interleukin-17 alpha (IL-17A), IL-23A, and IL-24, interferons (IFN) interferon alpha 1 (IFNA1) and interferon beta 1 (IFNB1), tumor necrosis factor (TNF) superfamily 4 (TNFSF4), transforming growth factor (TGF) superfamily, bone morphogenetic proteins 3 and 6 (BMP3 and BMP6), transforming growth factor beta 1 (TGFB1), and other growth factors, including macrophage colony-stimulating factor (M-CSF), C-fos-induced growth factor (FIGF), and platelet-derived growth factor alpha (PDGFA) polypeptide, in melioidosis patients compared to their expression in other sepsis cases, irrespective of comorbidities, duration of fever/clinical symptoms, and antibiotic treatment. Our findings indicate a dominant Th2- and Th17-type-cytokine response, suggesting that their dysregulation at initial stages of infection may play an important role in disease pathogenesis. IL-1A, interleukin-1 beta (IL-1B), and IL-8 were significantly downregulated in septicemic melioidosis patients compared to their expression in other sepsis cases. These differentially expressed genes may serve as biomarkers for melioidosis diagnosis and targets for therapeutic intervention and may help us understand immune response mechanisms. IMPORTANCE Melioidosis is a life-threatening infectious disease caused by a soil-associated Gram-negative bacterium, B. pseudomallei. Melioidosis is endemic in Southeast Asia and northern Australia; however, the global distribution of B. pseudomallei and the disease burden of melioidosisis are still poorly understood. Melioidosis is difficult to treat, as B. pseudomallei is intrinsically resistant to many antibiotics and requires a long course of antibiotic treatment. The mortality rates remain high in areas of endemicity, with reoccurrence being common. Therefore, it is imperative to diagnose the disease at an early stage and provide vital clinical care to reduce the mortality rate. With limitations in treatment and lack of a vaccine, it is crucial to study the immune response mechanisms to this infection to get a better understanding of disease susceptibility and pathogenesis. Therefore, this study aimed to analyze the gene expression levels of important cytokines to establish useful correlations for diagnostic and therapeutic purposes.

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Gene expression levels of growth hormone receptor and insulin-like growth factor-I in gonads of maturing coho salmon (Oncorhynchus kisutch)

Fish Physiology and Biochemistry ◽

10.1023/b:fish.0000030576.16255.64 ◽

2003 ◽

Vol 28 (1-4) ◽

pp. 335-336 ◽

Cited By ~ 10

Author(s):

Haruhisa Fukada ◽

Jon T. Dickey ◽

Andrew L. Pierce ◽

Nicholas Hodges ◽

Akihiko Hara ◽

...

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Growth Factor ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Coho Salmon ◽

Oncorhynchus Kisutch ◽

Expression Levels ◽

Factor I ◽

Gene Expression Levels

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Antibacterial Mechanism of 405-Nanometer Light-Emitting Diode against Salmonella at Refrigeration Temperature

Applied and Environmental Microbiology ◽

10.1128/aem.02582-16 ◽

2016 ◽

Vol 83 (5) ◽

Cited By ~ 25

Author(s):

Min-Jeong Kim ◽

Hyun-Gyun Yuk

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Light Emitting Diode ◽

Dna Oxidation ◽

Uptake System ◽

Antibacterial Mechanism ◽

Content Type ◽

Light Emitting ◽

Expression Levels ◽

Gene Expression Levels

ABSTRACT The aim of this study was to elucidate the antibacterial mechanism of 405 ± 5-nm light-emitting diode (LED) illumination against Salmonella at 4°C in phosphate-buffered saline (PBS) by determining endogenous coproporphyrin content, DNA oxidation, damage to membrane function, and morphological change. Gene expression levels, including of oxyR, recA, rpoS, sodA, and soxR, were also examined to understand the response of Salmonella to LED illumination. The results showed that Salmonella strains responded differently to LED illumination, revealing that S. enterica serovar Enteritidis (ATCC 13076) and S. enterica subsp. enterica serovar Saintpaul (ATCC 9712) were more susceptible and resistant, respectively, than the 16 other strains tested. There was no difference in the amounts of endogenous coproporphyrin in the two strains. Compared with that in nonilluminated cells, the DNA oxidation levels in illuminated cells increased. In illuminated cells, we observed a loss of efflux pump activity, damage to the glucose uptake system, and changes in membrane potential and integrity. Transmission electron microscopy revealed a disorganization of chromosomes and ribosomes due to LED illumination. The levels of the five genes measured in the nonilluminated and illuminated S. Saintpaul cells were upregulated in PBS at a set temperature of 4°C, indicating that increased gene expression levels might be due to a temperature shift and nutrient deficiency rather than to LED illumination. In contrast, only oxyR in S. Enteritidis cells was upregulated. Thus, different sensitivities of the two strains to LED illumination were attributed to differences in gene regulation. IMPORTANCE Bacterial inactivation using visible light has recently received attention as a safe and environmentally friendly technology, in contrast with UV light, which has detrimental effects on human health and the environment. This study was designed to understand how 405 ± 5-nm light-emitting diode (LED) illumination kills Salmonella strains at refrigeration temperature. The data clearly demonstrated that the effectiveness of LED illumination on Salmonella strains depended highly on the serotype and strain. Our findings also revealed that its antibacterial mechanism was mainly attributed to DNA oxidation and a loss of membrane functions rather than membrane lipid peroxidation, which has been proposed by other researchers who studied the antibacterial effect of LED illumination by adding exogenous photosensitizers, such as chlorophyllin and hypericin. Therefore, this study suggests that the detailed antibacterial mechanisms of 405-nm LED illumination without additional photosensitizers may differ from that by exogenous photosensitizers. Furthermore, a change in stress-related gene regulation may alter the susceptibility of Salmonella cells to LED illumination at refrigeration temperature. Thus, our study provides new insights into the antibacterial mechanism of 405 ± 5-nm LED illumination on Salmonella cells.

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Influence of Insulin-Like Growth Factor 1 Gene Expression in Women with Breast Cancer: A Systematic Review

10.21203/rs.3.rs-69892/v1 ◽

2020 ◽

Author(s):

Danylo Rafhael Costa-Silva ◽

Francisco Adelton Alves-Ribeiro ◽

Maria da Conceição Barros-Oliveira ◽

Larysse Cardoso Campos-Verdes ◽

Renato de Oliveira Pereira ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Systematic Review ◽

Growth Factor ◽

Expression Patterns ◽

Insulin Like Growth Factor ◽

Expression Levels ◽

Cancer Support ◽

Increased Risk ◽

Gene Expression Levels

Abstract Background: Breast cancer, the leading cause of cancer death among women worldwide, one of the major risk factors for breast cancer is genetic changes. Changes in the expression levels of the insulin-like growth factor 1 (IGF-1) gene have been associated with increased risk and aggressiveness of breast cancer. The IGF-1 gene encodes the IGF-1 peptide that is present in most human tissues, as in the normal and neoplastic mammary gland. Here, we conducted a systematic review to investigate the influence of IGF-1 gene expression levels in women with breast cancer.Methods: PubMed, Scopus, and Web of Science databases were searched for relevant studies published between February 2 and May 15, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find association between IGF-1gene expression and breast cancer.Results: A growing number of studies in women with breast cancer support, with controversial results, the influence of IGF-1 gene expression levels on clinical-pathological factors, disease-free survival, overall survival, and resistance to tamoxifen.Conclusions: Therefore, the elucidation of IGF-1 gene expression patterns through further studies may enable the characterization of women at high risk for breast cancer, as well as the development of effective prognostic and therapeutic strategies.

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Impact of gene expression of orotate phosphoribosyl transferase for complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4566 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4566-4566

Author(s):

T. Kajiwara ◽

T. Nishina ◽

I. Hyodo ◽

T. Moriwaki ◽

S. Endo ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Growth Factor ◽

Cell Carcinoma ◽

Squamous Cell ◽

Predictive Factor ◽

Complete Response ◽

Carcinoma Of The Esophagus ◽

Expression Levels ◽

Gene Expression Levels

4566 Background: Chemoradiotherapy (CRT) is a potential alternative to surgery in patients with squamous cell carcinoma of the esophagus. Complete response (CR) to CRT is essential for a good prognosis and there is a need for a predictive method of CR in CRT. Methods: The pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 41 patients treated with a definitive concurrent CRT (5-FU/CDDP and 60 Gy) for esophageal cancer (cStage II or III). cDNA was derived from tumor cells of biopsy specimens by the laser capture microdissection and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using fluorescence-based, real-time reverse transcription PCR. Gene expression levels of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase (OPRT), metylenetetrahydrofolate reductase, dihydrofolate reductase (DHFR), excision repair cross-complementing gene 1, vascular endothelial growth factor, epidermal growth factor receptor and matrix metalloproteinase 9 (MMP-9) were measured. Results: Median gene expression levels of OPRT and DHFR were significantly higher in CR patients (p=0.0206 and 0.0191, respectively). MMP-9 was significantly lower in CR patients (p=0.0436). When the median values of the gene expression levels were selected as the cutoff values, CR rate was significantly higher in the high OPRT group and high DHFR group (p=0.0104 and 0.0104, respectively). However, there was no statistical difference in CR rate between the low MMP-9 group and the high MMP-9 group. Multivariate analysis, including clinical stage and biomarkers, revealed that high OPRT gene expression was an independent predictive factor of CR (p=0.0329, relative risk=6.65, 95% confidence interval, 1.17–37.89%). Conclusions: The measurement of OPRT gene expression in tumor biopsies may be a predictive factor of CR to CRT in patients with squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.

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Effects of Selenium Supplementation on Gene Expression Levels of Inflammatory Cytokines and Vascular Endothelial Growth Factor in Patients with Gestational Diabetes

Biological Trace Element Research ◽

10.1007/s12011-017-1045-8 ◽

2017 ◽

Vol 181 (2) ◽

pp. 199-206 ◽

Cited By ~ 7

Author(s):

Mehri Jamilian ◽

Mansooreh Samimi ◽

Faraneh Afshar Ebrahimi ◽

Esmat Aghadavod ◽

Robabeh Mohammadbeigi ◽

...

Keyword(s):

Gene Expression ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Gestational Diabetes ◽

Inflammatory Cytokines ◽

Selenium Supplementation ◽

Vascular Endothelial ◽

Expression Levels ◽

Endothelial Growth Factor ◽

Gene Expression Levels

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The effects of conifer polyprenol nanoemulsions on skin cell culture proliferation rate and gene expression levels of structural proteins, growth factor and inflammatory cytokines

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.wcp2018.0_po3-10-18 ◽

2018 ◽

Vol WCP2018 (0) ◽

pp. PO3-10-18

Author(s):

Ilona Vanaga ◽

Janis Ancans ◽

Ilze Blake ◽

Ugis Kletnieks ◽

Jerzy Gubernator

Keyword(s):

Gene Expression ◽

Cell Culture ◽

Growth Factor ◽

Inflammatory Cytokines ◽

Proliferation Rate ◽

Structural Proteins ◽

Expression Levels ◽

Skin Cell ◽

Gene Expression Levels

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Influence of Insulin-Like Growth Factor 1 Gene Expression in Women with Breast Cancer: A Systematic Review

10.21203/rs.3.rs-104528/v1 ◽

2020 ◽

Author(s):

Danylo Rafhael Costa-Silva ◽

Maria da Conceição Barros-Oliveira ◽

Larysse Cardoso Campos-Verdes ◽

Renato de Oliveira Pereira ◽

Cleciton Braga Tavares ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Systematic Review ◽

Growth Factor ◽

Expression Patterns ◽

Insulin Like Growth Factor ◽

Expression Levels ◽

Cancer Support ◽

Increased Risk ◽

Gene Expression Levels

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Molecular Determinants of Cetuximab Efficacy

Journal of Clinical Oncology ◽

10.1200/jco.2005.09.100 ◽

2005 ◽

Vol 23 (15) ◽

pp. 3536-3544 ◽

Cited By ~ 166

Author(s):

Daniel Vallböhmer ◽

Wu Zhang ◽

Michael Gordon ◽

Dong Yun Yang ◽

Jim Yun ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Growth Factor ◽

Clinical Outcome ◽

Single Agent ◽

Rank Test ◽

Expression Levels ◽

Log Rank Test ◽

Cox 2 ◽

Gene Expression Levels

Purpose To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. Patients and Methods Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. Results There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. Conclusion This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.

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