Biomarker Insights最新文献

Chronic pruritus of unknown origin (CPUO) is a refractory condition. The expression of Interleukin-31 (IL-31), a major pruritogenic cytokine, in CPUO patients has not been investigated. This study aimed to investigate the potential association of IL-31 with CPUO. This was a cross-sectional, analytical study. Patients diagnosed with CPUO and healthy subjects were included at a ratio of 1:2. Serum IL-31 levels were measured in both groups and compared. There were 10 CPUO and 20 healthy subjects who participated in this study. The median IL-31 level in the CPUO group was significantly higher than in the healthy group (127.3 vs 34.4 pg/mL; P < .001). The presence of CPUO was independently associated with IL-31 levels with a coefficient of 89.678 (P < .001). The serum IL-31 cutoff point for CPUO was 56.8 pg/mL, with an area under the receiver operating characteristic curve (ROC) of 100%. Chronic pruritus of unknown origin was significantly and independently associated with higher IL-31 levels. Further clinical trials of IL-31-related treatment may be justified in CPUO patients.

Background: Human saliva has been identified as a novel, practical, and noninvasive source of biomarkers and genetic materials. However, it is equally challenging due to the availability of an abundance of impurities in the form of microbes and other proteinaceous compounds. The objective of this study was to develop a robust, reproducible, and economic method of extracting high-yield and high-quality RNA from whole human saliva.

Methods: The modified TRIzol protocol was developed to extract RNA from saliva (n = 14), followed by complementary DNA synthesis and reverse transcription quantitative polymerase chain reaction analyses for the genes encoding IL1B, ALPL, RUNX2, and ACTB. To compare our protocol with the spin column-based method, we used Qiagen Salivary Protect Micro-RNA spin columns (n = 6). To evaluate and compare the yields and quality of extracted RNAs from both methods, we used (1) Experion Bioanalyzer, (2) QuantiFluor RNA dye, and (3) NanoDrop 2000 Spectrometer.

Results: With the modified TRIzol lysis protocol, a high yield of total RNA, on average 12.34 μg, from saliva was extracted compared with on average 0.2 μg with a spin column-based method. The average RQI (RNA quality index) with the TRIzol method was 7.86, which is also comparable with that of the spin column-based method (RQI = 7.58). QuantiFluor dye used for RNA quantification showed a 16-fold higher yield of RNA concentration using our TRIzol protocol.

Conclusions: Our modified TRIzol protocol is a reproducible method to extract RNA from whole human saliva which can be used for gene expression analysis. This method allows also ensures the quality of RNA required for specific applications such as RNA sequencing.

Introduction: Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially considered as a nonfunctional peptide, soon after, UAG has been associated to an insulin sensitizing action and to a negative action on energy balance. The aim of this study was to analyze the association between the serum levels of UAG and glucose metabolism parameters in obese women, independently from eventual influence of anthropometrics.

Methods: One hundred lean and 254 obese Caucasian women were studied. Each woman was characterized for anthropometrics, fasting glucose, insulin, HbA1c, and UAG. In addition, obese women were subjected to a classic oral glucose tolerance test (oGTT) to assess glucose and insulin at 120 minutes. Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR). Obese women were classified in 3 glycemic status subgroups (normoglycemia, prediabetes, and diabetes) according to HbA1c and to fasting and oGTT glucose values.

Results: In comparison with the lean group, significantly lower levels of UAG were observed in obese women. However, no significant difference was observed through obesity classes I to III. UAG levels were not significantly different among glycemic status subgroups and did not show any association with glucose, insulin, HOMA-IR, or HbA1c.

Conclusions: Although anthropometry can influence the level of the unacylated form of ghrelin, UAG plasma levels do not associate to glucose homeostasis parameters.

Background: Bacteremia and sepsis are significant contributors to the morbidity, mortality, and economic burden of health care systems worldwide. Procalcitonin has been identified as a potentially useful marker of disease and severity in sepsis. However, the assumption that greater procalcitonin levels correlate with greater burden of disease has not been adequately studied.

Methods: A retrospective chart review of adult patients admitted to an urban teaching hospital with suspected sepsis was undertaken to test the association of elevated procalcitonin (>30 ng/mL) with other markers of sepsis (lactic acid, white blood cell count, percent bands), severity of disease (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation-II [APACHE II] scores), and mortality.

Results: In total, 168 patients were identified over 18 months (42% ward, 11% Stepdown, 44% medical intensive care unit [MICU], 2% surgical intensive care unit (STICU), 1% gynecology [GYN]). The Spearman correlation analysis showed that serum procalcitonin level did not correlate with SOFA (P = .238) or APACHE II (P = .918) scores on admission, and did not correlate with survival (Kruskal-Wallis test, P = .937). However, higher serum procalcitonin levels were associated with patients who had positive blood cultures (Kruskal-Wallis test, P = .0016 for Gram-positive and P = .0007 for Gram-negative bacteria). Lactic acid levels on admission strongly correlated with SOFA APACHE II (the Spearman correlation, P < .0001 for both) and mortality (P = .0001 for both).

Conclusions: Higher serum procalcitonin levels above 30 ng/mL failed to correlate with indicators of sepsis, severity of disease (SOFA and APACHE II scores), and mortality but were associated with positive blood cultures. Lactic acid levels did show correlation to both severity of disease and mortality. Serum procalcitonin levels >30 ng/mL do not appear to correlate with the severity of disease in a sample of patients with markedly elevated initial procalcitonin levels.

Allostatic load, or the physiological dysregulation accumulated due to senescence and stress, is an established predictor of human morbidity and mortality and has been proposed as a tool for monitoring health and welfare in captive wildlife. It is estimated by combining biomarkers from multiple somatic systems into allostatic load indices (ALIs), providing a score representing overall physiological dysregulation. Such ALIs have been shown to predict disease and mortality risk in western lowland gorillas. In these prior analyses, we were unable to include lipid markers, a potential limitation as they are key biomarkers in human models. Recently, we were able to assay serum cholesterol and triglycerides and add them to our previous ALI. We then re-examined associations with health outcomes using binomial generalized linear models. We constructed ALIs using 2 pooling strategies and 2 methods. By itself, a 1-unit increase in allostatic load was associated with higher odds of all-cause morbidity and mortality, but results were mixed for cardiac disease. However, the best fit models for all-cause morbidity and cardiac disease included only age and sex. Allostatic load was retained alongside age in the best fit models for mortality, with a 1-unit increase associated with 23% to 45% higher odds of death. Compared with previous results, ALIs containing cholesterol and triglycerides better predict disease risk in zoo-housed western lowland gorillas, as evidenced by larger effect sizes for some models and better goodness of fit for all ALIs. Based on these results, we address methodology for future allostatic load research on wildlife.

Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status, thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy test that uses flow cytometry-based immunophenotyping and artificial neural network (ANN) analysis to detect PCa. Numerous myeloid and lymphoid cell populations, including myeloid-derived suppressor cells, were measured from 156 patients with PCa, 123 with benign prostatic hyperplasia (BPH), and 99 male healthy donor (HD) controls. Using pattern recognition neural network (PRNN) analysis, a type of ANN, PCa detection compared against HD resulted in 96.6% sensitivity, 87.5% specificity, and an area under the curve (AUC) value of 0.97. Detecting patients with higher risk disease (⩾Gleason 7) against lower risk disease (BPH/Gleason 6) resulted in 92.0% sensitivity, 42.7% specificity, and an AUC of 0.72. This study suggests that analyzing flow cytometry immunophenotyping data with PRNNs may prove to be a useful tool to improve PCa detection and reduce the number of unnecessary prostate biopsies performed each year.

This editorial announces the new Biomarker Insights Editor-in-Chief. The journal will continue to publish high-quality original reports and review articles in all areas of biomarker research, and will welcome submissions that focus on improving the quality of the biomarker research literature.

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with susceptibility to autoimmune diseases. The functional polymorphism in PTPN22 at 1857 is a strong risk factor for vitiligo susceptibility in Europeans; however, controversy exits in other populations. Present study was aimed to determine whether the PTPN22 C1857T polymorphism confers susceptibility to vitiligo in Saudi Arabians. Genomic DNA was extracted and amplified using tetra primer amplification-refractory mutation system polymerase chain reaction (ARMS-PCR) method. The frequencies of allele T and genotype CT of PTPN22 C1858T polymorphism were significantly higher, whereas those of allele C and genotype CC were lower in patients as compared with controls (P < 0.0001). The genotype TT was absent in both the patients and controls. It is concluded that PTPN22 C1858T polymorphism is strongly associated with vitiligo susceptibility. However, additional studies are warranted using large number of samples from different ethnicities and geographical areas.

Purpose: Postischemic reperfusion injury may exacerbate cerebral damage and capillary dysfunction, leading to brain edema (BE), hemorrhagic transformation (HT), necrosis, and injury from free radicals with subsequent infarct growth (IG). Several plasmatic biomarkers involved in the ischemic cascade have been studied in relation to radiological and clinical outcomes of reperfusion injury in ischemic stroke with heterogeneous results. This article provides a brief overview of the contribution of circulating biomarkers to the pathophysiology of parenchymal damage in ischemic stroke patients treated with revascularization therapies.

Methods: We included full reports with measurements of plasma markers in patients with acute ischemic stroke treated with revascularization therapies.

Findings: Our research included a large number of observational studies investigating a possible role of circulating biomarkers in the development of parenchymal damage after acute stroke treatments. To make the results clearer, we divided the review in 4 sections, exploring the relation of different biomarkers with each of the indicators of parenchymal damage (HT, BE, IG, recanalization).

Discussion and conclusion: Definite conclusions are difficult to draw because of heterogeneity across studies. However, our review seems to confirm an association between some circulating biomarkers (particularly matrix metalloproteinase-9) and occurrence of parenchymal damage in ischemic stroke patients treated with revascularization therapies.

Background: Human B-cell responses are regulated through synergy between a collection of activation and inhibitory receptors. Fc receptor-like (FCRL) molecules have recently been identified as co-receptors that are preferentially expressed in human B-cells, which may also play an important role in the regulation of human B-cell responses. FCRL1 is a member of the FCRL family molecules with 2 immunoreceptor tyrosine-based activation motifs (ITAMs) in its cytoplasmic tail. This study aimed to investigate the regulatory roles of FCRL1 in human B-cell responses.

Materials and methods: The regulatory potential of FCRL1 in human B-cell through knockdown of FCRL1 expression in the Ramos and Daudi Burkitt lymphoma (BL) cell lines by using the retroviral-based short hairpin ribonucleic acid (shRNA) delivery method. The functional consequences of FCRL1 knockdown were assessed by measuring the proliferation, apoptosis, and the expression levels of Bcl-2, Bid, and Bax genes as well as phosphoinositide-3 kinase/-serine-threonine kinase AKT (PI3K/p-AKT) pathway in the BL cells, using the quantitative real-time polymerase chain reaction (PCR) and flow cytometry analysis. The NF-κB activity was also measured by the enzyme-linked immunosorbent assay (ELISA).

Results: FCRL1 knockdown significantly decreased cell proliferation and increased apoptotic cell death in the BL cells. There was a significant reduction in the extent of the Bcl-2 gene expression in the treated BL cells compared with control cells. On the contrary, FCRL1 knockdown increased the expression levels of Bid and Bax genes in the treated BL cells when compared with control cells. In addition, the extent of the PI3K/p-AKT expression and phosphorylated-p65 NF-κB activity was significantly decreased in the treated BL cells compared with control cells.

Conclusions: These results suggest that FCRL1 can play a key role in the activation of human B-cell responses and has the potential to serve as a target for immunotherapy of FCRL1 positive B-cell-related disorders.