Usefulness of copeptin as a potential biomarker in TBE

Objective: The aim of the study was to evaluate the usefulness of copeptin for differentiation of hyponatremia in the course of tick-borne encephalitis (TBE) and for being a prognostic marker of the severity of TBE.

Materials and methods: One hundred and fourteen patients with TBE were included in the study. The control group consisted of 62 patients diagnosed with viral meningitis.

Results: Copeptin concentration did not differ in patients with hyponatremia and normonatremia. Urinary sodium excretion to plasma copeptin (copeptin/UNa Secretion) ratio was significantly lower in Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion patients than in patients with hyponatremia of other origin. Mean copeptin concentration in TBE patients was higher than in control group (VM) patients. There were no differences between patients with severe and mild course of TBE.

Conclusions: Copeptin/UNa ratio may be used as a potential biomarker of SIADH in patients with TBE. Copeptin concentration is significantly higher in patients with TBE than in viral meningitis of other origin, especially in patients aged 18–34 and >49 years old. Copeptin does not differentiate TBE of mild and severe course.     

Galectin-10, a potential biomarker of eosinophilic airway inflammation

Measurement of eosinophilic airway inflammation can assist in the diagnosis of allergic asthma and in the management of exacerbations, however its clinical implementation remains difficult. Galectin-10 has been associated with eosinophilic inflammation and has the potential to be used as a surrogate biomarker. This study aimed to assess the relationship between galectin-10 in sputum with sputum eosinophil counts, the current gold standard of eosinophil inflammation in the lung. Thirty-eight sputum samples were processed for both eosinophil counts by cytospins and semi-quantitative measurements of galectin-10 by western blots. A strong association was observed between galectin-10 levels in sputum and sputum eosinophil measurements, and they accurately determined sputum eosinophilia. The results support the potential for galectin-10 to be used as a surrogate biomarker of eosinophilic airway inflammation.     

Serum lactate as a novel potential biomarker in multiple sclerosis

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease associated with a probably secondary progressive neurodegenerative component. Impaired mitochondrial functioning has been hypothesized to drive neurodegeneration and to cause increased anaerobic metabolism in MS. The aim of our multicentre study was to determine whether MS patients had values of circulating lactate different from those of controls. Patients (n = 613) were recruited, assessed for disability and clinically classified (relapsing–remitting, secondary progressive, primary progressive) at the Catholic University of Rome, Italy (n = 281), at the MS Centre Amsterdam, The Netherlands (n = 158) and at the S. Camillo Forlanini Hospital, Rome, Italy (n = 174). Serum lactate levels were quantified spectrophotometrically with the analyst being blinded to all clinical information. In patients with MS serum lactate was three times higher (3.04 ± 1.26 mmol/l) than that of healthy controls (1.09 ± 0.25 mmol/l, p < 0.0001) and increased across clinical groups, with higher levels in cases with a progressive than with a relapsing–remitting disease course. In addition, there was a linear correlation between serum lactate levels and the expanded disability scale (EDSS) (R² = 0.419; p < 0.001). These data support the hypothesis that mitochondrial dysfunction is an important feature in MS and of particular relevance to the neurodegenerative phase of the disease. Measurement of serum lactate in MS might be a relative inexpensive test for longitudinal monitoring of “virtual hypoxia” in MS and also a secondary outcome for treatment trials aimed to improve mitochondrial function in patients with MS.     

IRF1 as a potential biomarker in Mycobacterium tuberculosis infection

Pulmonary tuberculosis (PTB) is a major global public health problem. The purpose of this study was to find biomarkers that can be used to diagnose tuberculosis. We used four NCBI GEO data sets to conduct analysis. Among the four data sets, GSE139825 is lung tissue microarray, and GSE83456 , GSE19491 and GSE50834 are blood microarray. The differential genes of GSE139825 and GSE83456 were 68 and 226, and intersection genes were 11. Gene ontology (GO) analyses of 11 intersection genes revealed that the changes were mostly enriched in regulation of leucocyte cell-cell adhesion and regulation of T-cell activation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs revealed that the host response in TB strongly involves cytokine-cytokine receptor interactions and folate biosynthesis. In order to further narrow the range of biomarkers, we used protein-protein interaction to establish a hub gene network of two data sets and a network of 11 candidate genes. Eventually, IRF1 was selected as a biomarker. As validation, IRF1 levels were shown to be up-regulated in patients with TB relative to healthy controls in data sets GSE19491 and GSE50834 . Additionally, IRF1 levels were measured in the new patient samples using ELISA. IRF1 was seen to be significantly up-regulated in patients with TB compared with healthy controls with an AUC of 0.801. These results collectively indicate that IRF1 could serve as a new biomarker for the diagnosis of pulmonary tuberculosis.     

Calreticulin as a potential diagnostic biomarker for lung cancer

Calreticulin (CRT) is an endoplasmic reticulum luminal Ca(2+)-binding chaperone protein. By immunizing mice with recombinant fragment (rCRT/39-272), six clones of monoclonal antibodies (mAbs) were generated and characterized. Based on these mAbs, a microplate chemiluminescent enzyme immunoassay (CLEIA) system with a measured limit of detection of 0.09?ng/ml was developed. Using this CLEIA system, it was found that soluble CRT (sCRT) level in serum samples from 58 lung cancer patients was significantly higher than that from 40 healthy individuals (only 9 were detectable, P?相似文献   

Liquid biopsy: miRNA as a potential biomarker in oral cancer

Oral cancer is one of the leading cancers in South-Asian countries. Despite the easy access of the oral cavity, the detection and five year survival rates of OSCC patients are dismal. Identification of non-invasive biomarkers to determine the progression and recurrence of OSCC could be of immense help to patients. Recent studies on oral cancer suggest the importance of non-invasive biomarker development. Micro-RNAs (miRNAs) are one of the important components of the cell-free nucleic acids available in different body fluids. Here, we have reviewed the current understanding of circulating miRNAs as non-invasive biomarkers in different body fluids of oral cancer patients. A number of circulating miRNAs are found to be common in the body fluids of OSCC patients, while many of these are study specific, the possible sources of this variability could be due to differences in sample processing, assay procedure, clinical stage of the disease, oral habit and environmental factors. The prognostic and therapeutic significance of these circulating miRNAs are suggested by several studies. Mir-371, mir-150, mir-21 and mir-7d were found to be potential prognostic markers, while mir-134, mir-146a, mir-338 and mir-371 were associated with metastases. The prognostic markers, mir-21 and mir-7d were also found to be significantly correlated with resistance to chemotherapy, while mir-375, mir-196 and mir-125b were significantly correlated with sensitivity to radiotherapy. Despite the promising roles of circulating miRNAs, challenges still remain in unravelling the exact regulation of these miRNAs before using them for targeted therapy.     

Regucalcin as a potential biomarker for metabolic and neuronal diseases

Regucalcin was initially discovered in 1978 as a regulatory protein in calcium signaling. The regucalcin gene, which is localized on the X chromosome, is found in vertebrate and invertebrate species. Regucalcin has been shown to play a pivotal role in cell regulation: maintaining of intracellular calcium homeostasis, suppressions of signal transduction, inhibition of translational protein synthesis, nuclear deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis, regulation of gene expression, and anti-effects on proliferation and apoptosis in many cell types. The expression of the regucalcin gene and its protein has been shown to alter with various metabolic diseases, and regucalcin plays an important role in the development of many pathophysiologic states. Serum regucalcin has been found to increase with liver injury, and also urinary regucalcin is elevated with kidney damage, suggesting a useful tool as biomarker for diagnosis. Moreover, regucalcin has been shown to be good tool in early diagnosis for Alzheimer’s disease and other brain diseases. This review will discuss a significance of regucalcin as a clinical biomarker in various diseases.     

The metabolome as a biomarker of aging in Drosophila melanogaster

Many biomarkers have been shown to be associated not only with chronological age but also with functional measures of biological age. In human populations, it is difficult to show whether variation in biological age is truly predictive of life expectancy, as such research would require longitudinal studies over many years, or even decades. We followed adult cohorts of 20 Drosophila Genetic Reference Panel (DGRP) strains chosen to represent the breadth of lifespan variation, obtain estimates of lifespan, baseline mortality, and rate of aging, and associate these parameters with age‐specific functional traits including fecundity and climbing activity and with age‐specific targeted metabolomic profiles. We show that activity levels and metabolome‐wide profiles are strongly associated with age, that numerous individual metabolites show a strong association with lifespan, and that the metabolome provides a biological clock that predicts not only sample age but also future mortality rates and lifespan. This study with 20 genotypes and 87 metabolites, while relatively small in scope, establishes strong proof of principle for the fly as a powerful experimental model to test hypotheses about biomarkers and aging and provides further evidence for the potential value of metabolomic profiles as biomarkers of aging.     

A novel mechanism for the regulation of IFN-gamma inducible protein-10 expression in rheumatoid arthritis

Chemokines play an essential role in the progression of rheumatoid arthritis (RA). In the present study we examined the expression and regulatory mechanisms of IFN-gamma inducible protein (IP)-10 in RA synovitis. RA synovial fluid contained greater amounts of IP-10 than did synovial fluid from patients with osteoarthritis. Immunolocalization analysis indicated that IP-10 was associated mainly with infiltrating macrophage-like cells, and fibroblast-like cells in the RA synovium. The interaction of activated leukocytes with fibroblast-like synoviocytes resulted in marked increases in IP-10 expression and secretion. Moreover, induction of IP-10 was mediated via specific adhesion molecules, as indicated by the finding that both anti-integrin (CD11b and CD18) and intercellular adhesion molecule-1 antibodies significantly inhibited IP-10 induction. These results suggest that IP-10 expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leukocytes with fibroblast-like synoviocytes, and that IP-10 may contribute to the recruitment of specific subpopulations of T cells (Th1 type) from the bloodstream into the synovial joints.     

BMI-1 autoantibody as a new potential biomarker for cervical carcinoma

BMI-1 is overexpressed in a variety of cancers, which can elicit an immune response leading to the induction of autoantibodies. However, BMI-1 autoantibody as a biomarker has seldom been studied with the exception of nasopharyngeal carcinoma. Whether BMI-1 autoantibodies can be used as a biomarker for cervical carcinoma is unclear. In this study,BMI-1 proteins were isolated by screening of a T7 phage cDNA library from mixed cervical carcinoma tissues. We analyzed BMI-1 autoantibody levels in serum samples from 67 patients with cervical carcinoma and 65 controls using ELISA and immunoblot. BMI-1 mRNA or protein levels were over-expressed in cervical carcinoma cell lines. Immunoblot results exhibited increased BMI-1 autoantibody levels in patient sera compared to normal sera. Additionally, the results for antibody affinity assay showed that there was no difference between cervical polyps and normal sera of BMI-1 autoantibody levels, but it was significantly greater in patient sera than that in normal controls (patient 0.827±0.043 and normal 0.445±0.023; P<0.001). What''s more, the levels of BMI-1 autoantibody increased significantly at stage I (0.672±0.019) compared to normal sera (P<0.001), and levels of BMI-1 autoantibodies were increased gradually during the tumor progression (stage I 0.672±0.019; stage II 0.775 ±0.019; stage III 0.890 ±0.027; stage IV 1.043±0.041), which were significantly correlated with disease progression of cervical carcer (P<0.001). Statistical analyses using logistic regression and receiver operating characteristics (ROC) curves indicated that the BMI-1 autoantibody level can be used as a biomarker for cervical carcinoma (sensitivity 0.78 and specificity 0.76; AUC = 0.922). In conclusion, measuring BMI-1 autoantibody levels of patients with cervical cancer could have clinical prognostic value as well as a non-tissue specific biomarker for neoplasms expressing BMI-1.     

Hydrogen peroxide in urine as a potential biomarker of whole body oxidative stress

The level of hydrogen peroxide (H2O2) in urine has been suggested as a potential biomarker of whole body oxidative stress, but issues of stability, reproducibility and biological variation have not been investigated to date. In this study, we used a refined protocol, which demonstrated improved sensitivity and precision, to determine the stability of H2O2 in urine, and to measure its concentration in apparently healthy subjects. We also investigated intra-individual variation within and between days. Results showed that H2O2 in urine is stable for up to 48 h at 4 degrees C, however, storage of urine at room temperature was associated with up to 50% increase in H2O2 concentration over a few hours. Total H2O2 in freshly voided urine from 55 healthy, fasting subjects ranged from 0.84 to 5.71 microM, or 90-1164 micromol H2O2/mol creatinine. Intra-individual variation was wide. Even when concentration corrected and collected at the same time of day, 2- to 3-fold variation was seen over 4 consecutive days, and over the course of a single day the creatinine-corrected H2O2 also varied significantly. We suggest that this large biological variation limits the usefulness of urine H2O2 as a biomarker of oxidative stress, the exception being when the effects of disease, therapy or diet induce very large changes in its concentration.     

ICAM-1 expression in vaginal cells as a potential biomarker for inflammatory response

This study aimed to elucidate the mechanisms that may lead to an efficient strategy to induce a suitable host response of the vaginal mucosa upon exposure to intravaginally delivered exogenous compounds. It was hypothesized that the upregulation of intercellular adhesion molecule (ICAM)-1 gene expression may reflect the inflammatory response evoked by exogenous compounds. Major emphasis was placed on ethylenediamine tetraacetic acid (EDTA) which was added as a synergistic agent to conventional spermicidal agents or anti-HIV drugs. The levels of ICAM-1 mRNA were examined as a surrogate marker for inflammatory response in human vaginal epithelial cells upon exposure to EDTA or interleukin (IL)-1β (i.e. positive control, 25 mM). The effects of estrogen on EDTA-induced ICAM-1 expression were also evaluated for the estrogen involvement in the inflammatory process of the vaginal mucosa. ICAM-1 expression in human vaginal cells (VK2/E6E7 cells) increased as EDTA concentration added to human vaginal cell lines increased. The effects of estrogen on EDTA-induced ICAM-1 expression in human vaginal epithelial cells were estrogen-concentration dependent; estrogen at lower concentrations (∼1-10 nM) did not affect ICAM-1 expression, whereas estrogen at higher concentrations (∼100 nM-1 µM) attenuated ICAM-1 expression. The influence of estrogen in ICAM-1 expression suggests the beneficial effects of estrogen on the regulation of vaginal homeostasis. Identification and quantification of specific surrogate markers for the inflammatory response evoked by exogenous compounds and their regulation by estrogen will lead to an efficient strategy against sexually transmitted diseases including AIDS.     

ICAM-1 expression in vaginal cells as a potential biomarker for inflammatory response

This study aimed to elucidate the mechanisms that may lead to an efficient strategy to induce a suitable host response of the vaginal mucosa upon exposure to intravaginally delivered exogenous compounds. It was hypothesized that the upregulation of intercellular adhesion molecule (ICAM)-1 gene expression may reflect the inflammatory response evoked by exogenous compounds. Major emphasis was placed on ethylenediamine tetraacetic acid (EDTA) which was added as a synergistic agent to conventional spermicidal agents or anti-HIV drugs. The levels of ICAM-1 mRNA were examined as a surrogate marker for inflammatory response in human vaginal epithelial cells upon exposure to EDTA or interleukin (IL)-1β (i.e. positive control, 25 mM). The effects of estrogen on EDTA-induced ICAM-1 expression were also evaluated for the estrogen involvement in the inflammatory process of the vaginal mucosa. ICAM-1 expression in human vaginal cells (VK2/E6E7 cells) increased as EDTA concentration added to human vaginal cell lines increased. The effects of estrogen on EDTA-induced ICAM-1 expression in human vaginal epithelial cells were estrogen-concentration dependent; estrogen at lower concentrations (～1–10 nM) did not affect ICAM-1 expression, whereas estrogen at higher concentrations (～100 nM–1 µM) attenuated ICAM-1 expression. The influence of estrogen in ICAM-1 expression suggests the beneficial effects of estrogen on the regulation of vaginal homeostasis. Identification and quantification of specific surrogate markers for the inflammatory response evoked by exogenous compounds and their regulation by estrogen will lead to an efficient strategy against sexually transmitted diseases including AIDS.     

Clinical utility of decorin in follicular fluid as a biomarker of oocyte potential

This study investigated the concentration of decorin (DCN) in mature follicular fluid and the existence in the granulosa cells. It also investigated whether DCN is useful as a biomarker for outcomes of assisted reproductive technology (ART). A retrospective cohort study was performed involving 130 oocytes of 88 patients treated with ART because of unexplained infertility. The concentration of DCN in the follicular fluid (F-DCN) was 39.26 ng/ml (median value); it was higher than that in serum. F-DCN of the oocytes fertilized by intracytoplasmic sperm injection (ICSI) was significantly lower than that of oocytes that were not fertilized (33.24 ng/ml vs 40.18 ng/ml; P = 0.043). When a cut-off level of 34.5 ng/ml was set according to the receiver-operating characteristic curve, the fertilization rate of the oocytes from the follicles in which F-DCN was lower than the cut-off level tended to be good compared to that of the oocytes with F-DCN higher than the cut-off level (P = 0.052). DCN is less likely to be produced by the granulosa cells (GCs), because it was not detected in GCs by immunostaining and Western blot analysis. F-DCN has a possibility to be a biomarker indicating the quality of oocytes collected from the corresponding follicle.     

Assessment of Ki-67 as a potential biomarker in patients with breast cancer

Breast cancer is the most common cancer in females, it accounts for one third of all malignancies affecting women. Appropriate biomarkers play significant role in predicting the prognosis and decide the specific therapy to each patient. In this study we aimed at evaluating the value of Ki-67 as a prognostic marker in breast cancer patients and to analyze the associations between Ki-67 and their clinicopathological parameters. This study included 92 patients with developed non metastatic breast cancer and 10 women had benign breast tumor served as controls. We measured the serum level by ELISA technique and tissue expression of Ki-67 by immunohistochemical technique. Our results showed that there were no statistically significant differences in serum Ki-67 levels between the two studied groups. As for Ki-67expression in breast cancer cells, the score increases with increase of tumor size, grade, premenopausal, Ki-67 expression in estrogen and progesterone receptor positive tumors showed lower values than estrogen and progesterone negative tumors, while higher Ki-67 expression was more frequently associated with HER2-positive. In conclusion; our study supports the finding that tissue Ki-67 expression may add prognostic information to that obtained from classical prognostic factors and can provide data of significant value to other important prognostic indicators such as pathological grading, and axillary lymph node involvement.     

Pirfenidone gel in patients with localized scleroderma: a phase II study

Introduction

Localized scleroderma is an inflammatory disease in its first stages and a fibrotic process in later stages, principally mediated by the transforming growth factor β. To date, there is no standard treatment. The objective of this study was to determine the effectiveness and safety of 8% pirfenidone gel in patients with localized scleroderma.

Methods

This was an open phase II clinical trial that included 12 patients. Treatment with pirfenidone was indicated, three times daily for 6 months. Patients were evaluated clinically with the modified Localized Scleroderma Skin Severity Index (mLoSSI), as well with a durometer and histologically using hematoxylin and eosin stain and Masson’s trichrome stain.

Results

The baseline mLoSSI average scores were 5.83 ± 4.80 vs. 0.83 ± 1.75 (P = 0.002) at 6 months. The initial durometer induration of the scleroderma plaques was 35.79 ± 9.10 vs. 32.47 ± 8.97 at 6 months (P = 0.05). We observed histopathological improvement with respect to epidermal atrophy, inflammation, dermal or adipose tissue fibrosis and annex atrophy from 12.25 ± 3.25 to 9.75 ± 4.35 (P = 0.032). The 8% pirfenidone gel application was well tolerated, and no side effects were detected.

Conclusions

This is the first study on the therapeutic use of pirfenidone gel in localized scleroderma. It acts on both the inflammatory and the fibrotic phases. Considering its effectiveness, good safety profile and the advantage of topical application, pirfenidone is a treatment option in this condition.     

Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction

Recent studies have revealed the role of microRNAs (miRNAs) in a variety of basic biological and pathological processes and the association of miRNA signatures with human diseases. Circulating miRNAs have been proposed as sensitive and informative biomarkers for multiple cancers diagnosis. We have previously documented aberrant up-regulation of miR-1 expression in ischemic myocardium and the consequent slowing of cardiac conduction. However, whether miR-1 could be a biomarker for predicting acute myocardial infarction (AMI) is unclear. In the present study, we recruited 159 patients with or without AMI for quantification of miR-1 level in plasma using real-time RT-PCR method. We performed Wilcoxon rank sum and signed rank tests for comparison. Univariable linear regression and logistics regression analyses were performed to assess the potential correlation between miR-1 and known AMI markers. We also conducted receiver-operator characteristic curve (ROC) analysis to evaluate the diagnostic ability of miR-1. We found that: miR-1 level was significantly higher in plasma from AMI patients compared with non-AMI subjects and the level was dropped to normal on discharge following medication. Increased circulating miR-1 was not associated with age, gender, blood pressure, diabetes mellitus or the established biomarkers for AMI. However, miR-1 level was well correlated with QRS by both univariable linear and logistics regression analyses. The area under ROC curve (AUC) was 0.7740 for separation between non-AMI and AMI patients and 0.8522 for separation AMI patients under hospitalization and discharge. Collectively, our results revealed that circulating miR-1 may be a novel, independent biomarker for diagnosis of AMI.