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Identification of Differential Intestinal Mucosa Transcriptomic Biomarkers for Ulcerative Colitis by Bioinformatics Analysis
Background. Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affect mucosal homeostasis and triggers inappropriate immune response. The purpose of the study was to identify significant biomarkers with potential therapeutic targets and the underlying mechanisms. Methods. The gene expression profiles of GSE48958, GSE73661, and GSE59071 are from the GEO database. Differentially expressed genes (DEGs) were screened by the GEO2R tool. Next, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then, protein-protein interaction (PPI) was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Results. There were a total of 128 common DEGs genes, including 86 upregulated genes enriched in extracellular space, regulation of inflammatory response, chemokine-mediated signaling pathway, response to lipopolysaccharide, and cell proliferation, while 42 downregulated genes enriched in the integral component of the membrane, the integral component of the plasma membrane, apical plasma membrane, symporter activity, and chloride channel activity. The KEGG pathway analysis results demonstrated that DEGs were particularly enriched in cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, pertussis, and rheumatoid arthritis. 18 central modules of the PPI networks were selected with Cytotype MCODE. Furthermore, 18 genes were found to significantly enrich in the extracellular space, inflammatory response, chemokine-mediated signaling pathway, TNF signaling pathway, regulation of cell proliferation, and immune response via reanalysis of DAVID. Conclusion. The study identified DEGs, key target genes, functional pathways, and pathway analysis of UC, which may provide potential molecular targets and diagnostic biomarkers for UC.
Clinical Characteristics of Patients with Different N-Terminal Probrain Natriuretic Peptide Levels after Hematopoietic Stem Cell Transplantation
Heart failure (HF) is not uncommon among patients with hematologic malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) and is associated with an increased mortality. Among HSCT patients without signs or symptoms of HF, groups with elevated and normal N-terminal probrain natriuretic peptide (NT-proBNP) levels have been poorly characterized in previous literature. Herein, we reviewed consecutive admissions for HM undergoing HSCT (). Based on NT-proBNP levels and clinical signs or symptoms of HF at follow-up (one month after HSCT), patients were grouped into ENPH (elevated , presence of HF symptoms or signs), ENAH (elevated , absence of HF symptoms or signs), and NN (normal ). ENPH, ENAH, and NN were observed in 22.9%, 54.5%, and 22.6% of patients, respectively. ENPH patients had a significantly higher baseline NT-proBNP level, followed by the ENAH and NN groups, respectively (). Frequencies of HLA partially matched related donors, stem cell source (bone marrow+peripheral blood), and utilization of graft-versus-host disease prophylaxis regimens (ciclosporin+methotrexate+antithymocyte globulin±mycophenolate mofetil) were also the highest in the ENPH group, followed by ENAH and NN groups, respectively (all ). Uric acid and hemoglobin levels, transplant type, and cyclophosphamide-based conditioning regimens utilized were similar between the ENAH and ENPH groups. We found that ENPH and ENAH are commonly observed in HM hospitalized for HSCT. Serum NT-proBNP levels may allow for earlier identification of HSCT patients at high risk of developing cardiac dysfunction.
Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Blood to Distinguish Lung Cancer Patients from Healthy Subjects
Objective. Inflammation-driven markers play a crucial role in tumorigenesis and tumor progression. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in blood are systemic inflammatory response markers. Some reports have showed that NLR and PLR are related to a poor prognosis in patients with lung cancer. However, little studies have reported whether NLR and PLR can be diagnostic markers for lung cancer. The aim of the current study is to investigate the roles of NLR and PLR in diagnosing lung cancer. Methods. This study analyzed data from lung cancer patients and healthy individuals in Wuxi People’s Hospital Affiliated with Nanjing Medical University. The Mann–Whitney test was performed to compare differences between the lung cancer group and the control group. Based on white blood cell (WBC) counts, both lung cancer patients and healthy individuals were divided into the low-level group, moderate-level group, and high-level group. The Kruskal-Wallis test was applied to compare differences of NLR and PLR among those groups with different WBC counts. Spearman correlation analysis was used to assess correlations. Receiver operating characteristic (ROC) curves were performed to determine diagnostic accuracy. Results. 210 patients diagnosed with lung cancer and 261 healthy subjects were enrolled in this study. Levels of NLR and PLR increased in the lung cancer group compared with the control group (). For the lung cancer group, NLR levels could rise with the increasing of WBC levels () while PLR levels had no significant variation with the increasing of WBC levels (). For the control group, NLR levels could rise with the increasing of WBC levels () while PLR levels would decline with the increasing of WBC levels (). In the lung cancer group, both NLR and PLR had no significant correlations with aspartate transaminase, urea, and glucose. The area under the curve (AUC) with 95% confidence interval (95% CI) of NLR and PLR to distinguish lung cancer patients from healthy subjects was, respectively, 0.684 (0.634-0.735) and 0.623 (0.571-0.674). When NLR and PLR were combined, AUC (95% CI) increased to 0.691 (0.642-0.740). Conclusions. NLR and PLR alone have moderate ability to distinguish lung cancer patients from healthy subjects. Furthermore, combination forms of NLR and PLR can improve diagnostic ability.
Noninvasive Biomarkers of Gut Barrier Function in Patients Suffering from Diarrhea Predominant-IBS: An Update
The intestinal barrier plays a crucial role in the absorption of nutrients and in preventing the entry of pathogenic microorganisms and toxic molecules. Several studies have shown a compromised intestinal barrier associated with low-grade inflammation in the small intestinal mucosa in celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). In light of these new data, IBS is no longer considered a functional disease but rather a heterogeneous syndrome that has yet to be carefully studied. Therefore, investigating the integrity and function of the intestinal barrier is now essential to improving knowledge of the pathophysiology of IBS-D and to improving the management of IBS-D patients. However, the study of the intestinal barrier must clarify some still unsolved methodological aspects and propose standardised assays before becoming a useful diagnostic tool. In this framework, this review will discuss data about the tests that noninvasively evaluate the integrity and functionality of the human intestinal barrier, paying particular attention to patients with IBS-D, in both clinical and research situations.
Identification of a Set of Genes Improving Survival Prediction in Kidney Renal Clear Cell Carcinoma through Integrative Reanalysis of Transcriptomic Data
Background. With an enormous amount of research concerning kidney cancer being conducted, various treatments have been applied to its cure. However, high recurrence and metastasis rates continue to pose a threat to the survival of patients with kidney renal clear cell carcinoma (KIRC). Methods. Data from The Cancer Genome Atlas were downloaded, and a series of analyses were performed, including differential analysis, Cox analysis, weighted gene coexpression network analysis, least absolute shrinkage and selection operator analysis, multivariate Cox analysis, survival analysis, and receiver operating characteristic curve and functional enrichment analysis. Results. A total of 5,777 differentially expressed genes were identified from the differential analysis. The Cox analysis showed 1,853 significant genes (). Weighted gene coexpression network analysis revealed that 226 genes in the module were related to clinical parameters, including Tumor-Node-Metastasis (TNM) staging. Least absolute shrinkage and selection operator and multivariate Cox analyses suggested that four genes (CDKL2, LRFN1, STAT2, and SOWAHB) had a potential function in predicting the survival time of patients with KIRC. Survival analysis uncovered that a high risk of these four genes was associated with an unfavorable prognosis. Receiver operating characteristic curve analysis further confirmed the accuracy of the risk score model. The analysis of clinicopathological parameters of the four identified genes revealed that they were associated with the progression of KIRC. Conclusion. The gene expression model consisting of CDKL2, LRFN1, STAT2, and SOWAHB is a promising tool for predicting the prognosis of patients with KIRC. The results of this study may provide insights into the diagnosis and treatment of KIRC.
IFN-γ Correlations with Pain Assessment, Radiological Findings, and Clinical Intercourse in Patient after Lumbar Microdiscectomy: Preliminary Study
Objectives. We investigated the influence of pain decrease after lumbar microdiscectomy on the interferon gamma (IFN-γ) serum level in patients with lumbar disc herniations. The study challenges the mechanism of sciatica pain and the role of IFN-γ in radicular pain development. Material and Methods. We performed clinical and immunoenzymatic assessment in a group of 27 patients with lumbar radicular pain due to disc herniations before and 3 months after surgery. Clinical status was assessed with the use of the Numeric Rating Scale (NRS), the Pain Rating Index and Pain Intensity Index of McGill Pain Questionnaire (SF-MPQ), the Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The plasma concentrations of IFN-γ were ascertained by an immunoenzymatic method. Results. We observe significant correlations between the results of the pain in the back region assessment NRS back scale after the surgery with the level of IFN-γ before the procedure (; ) and after the procedure (; ). These are moderate and positive correlations—the decrease in pain is correlated with the lower IFN-γ level. Additionally, there are significant correlations between the results of the PRI scale and the IFN-γ level. The PRI score before surgery correlates positively with IFN-γ after surgery (; ), and the PRI score after surgery correlates positively with IFN before surgery (; ) and after surgery (; ). All correlations are moderate in severity—severe pain before surgery correlates with a higher level of IFN-γ after surgery and also higher IFN-γ before surgery. There were significant differences in the IFN-γ level before (; ) and after (; ) surgery in the groups of patients with and without nerve compression. In the group of patients with nerve compression, the level of IFN-γ before and after surgery was lower. Conclusions. Less pain ratio after operation correlates with the level of IFN-γ. In the group of patients without significant nerve compression confirmed by MRI scans, the level of IFN-γ before and after surgery was higher than that in the group with nerve root compression.