Potential Blood Biomarkers Research Articles

A Model for Estimating a Predictive Score for Alzheimer’s Disease in Individuals with Family History

Introduction The insight in the ethiopathogenesis of Alzheimer’s disease(AD) suggests a slowly developing neurodegenerative process that starts 10 to 20 years before the clinical manifestation. Preventing or slowing the process of neuronal damage would be the state of the art in neuroscience, but the fist step is to identify individuals at risk, diagnose AD in the preclinical stage, develop preventive strategies and start treatment in the early disease course. Objectives Developing a model for estimating a predictive risk score for AD in individuals with family history for AD and . Material and Methods A battery of biochemical test for identifying LPL deficiency, serological biomarkers (alfa 2 macroglobulin, homocystein, complement factor H, interleukin-6), APO E genotyping and neuropsychological tests (Mini Mental State Examination-MMSE, Clinical Dementia Rating, and the novel Syndrome Kurz test) are performed in 50 individuals with family history for AD. Results The early stage ongoing research that our team is performing, gives optimistic insight in the first results by combining the presence of the examined serological biomarkers, the neuropsychological tests results and ApoE ɛ4 genotype, we estimate the risk score for developing AD. Conclusion Till now a list of potential blood biomarkers has been suggested but none of them has shown to be sensitive, nor specific in accurate preclinical AD diagnosing. We believe that by combing these tests, a risk score for individuals with family history of AD would be estimated, so that a prospective approach and preventive strategies could be developed.

Mir-106b for HCC patient management after therapy

Background: MicroRNAs (miRNAs) are regulatory noncoding RNAs. Their aberrant expression is observed in many diseases, including Hepatocellular carcinoma (HCC). They are stable in biological fluids making miRNAs promising class of potential non invasive blood biomarkers for patients’ follow-up. mir-106b is frequently de-regulated in HCC with a role in cell proliferation and migration. Recent findings reported a circulating mir-106b altered expression in HCC.

Influence of Collection Time on Hematologic and Immune Markers in the American Alligator (Alligator mississippiensis)

Crocodilians are important keystone species and indicators of environmental health. Much remains unknown, however regarding utility of field-collected crocodilian blood samples for ecologic assessments. Field sampling sites are also often distant to analysis centers, necessitating development of new techniques and panels of assays that will yield environmentally relevant data. Stability and viability of hematological and immunological indices have been of particular interest for linking ecosystem health to biomarkers in resident species. In this study, we investigated the effect of time at analysis post-blood sampling at 4 and 24 hr on a panel of potential biomarkers in alligator blood. Our results suggest alligator blood samples can be reliably evaluated for both hematologic and immunologic profile 24 hr after sampling.

Acute Kidney Injury: New Biomarkers

Acute kidney injury (AKI) has various triggers, such as ischemia, nephrotoxins, radiocontrast, and bacterial endotoxins. It occurs in about one-third of patients treated in the intensive care unit. There is a higher mortality in patients with AKI compared with their non-AKI counterparts. The diagnosis of AKI usually depends on serum creatinine (SCr) measurements. However, SCr is a delayed and unreliable indicator of AKI. The lack of early biomarkers has limited the ability to manage AKI. Fortunately, understanding the early stress response of the kidney to injury has resulted in the identification and validation of several potential novel urine and blood biomarkers. Recently, new biomarkers of AKI with more favorable characteristics than SCr have been identified and studied in various experimental and clinical settings. This article reviews the most well-established biomarkers of AKI.

Gastrointestinal Safety Pharmacology in Drug Discovery and Development.

Although the basic structure of the gastrointestinal tract (GIT) is similar across species, there are significant differences in the anatomy, physiology, and biochemistry between humans and laboratory animals, which should be taken into account when conducting a gastrointestinal (GI) assessment. Historically, the percentage of cases of drug attrition associated with GI-related adverse effects is small; however, this incidence has increased over the last few years. Drug-related GI effects are very diverse, usually functional in nature, and not limited to a single pharmacological class. The most common GI signs are nausea and vomiting, diarrhea, constipation, and gastric ulceration. Despite being generally not life-threatening, they can greatly affect patient compliance and quality of life. There is therefore a real need for improved and/or more extensive GI screening of candidate drugs in preclinical development, which may help to better predict clinical effects. Models to identify drug effects on GI function cover GI motility, nausea and emesis liability, secretory function (mainly gastric secretion), and absorption aspects. Both in vitro and in vivo assessments are described in this chapter. Drug-induced effects on GI function can be assessed in stand-alone safety pharmacology studies or as endpoints integrated into toxicology studies. In silico approaches are also being developed, such as the gut-on-a-chip model, but await further optimization and validation before routine use in drug development. GI injuries are still in their infancy with regard to biomarkers, probably due to their greater diversity. Nevertheless, several potential blood, stool, and breath biomarkers have been investigated. However, additional validation studies are necessary to assess the relevance of these biomarkers and their predictive value for GI injuries.

Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease.

The aim of this study was to investigate the changes in the protein, cholesterol, and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease (AD), and identify potential blood biomarkers of the disease. A total of 31 Chinese patients with AD and 31 aged-matched control subjects were selected. Lipid rafts were isolated from platelets using Optiprep gradient centrifugation. The protein content of lipid rafts was evaluated using Micro BCA assay, the cholesterol content using molecular probes, ganglioside GM1 content using colorimetry and dot-blotting analysis. The results showed that the cholesterol and ganglioside GM1 content of lipid rafts from platelets was significantly higher in patients with AD than aged-matched control subjects, whereas the protein content of lipid rafts did not show any differences between the 2 groups. These results indicate that the increases in the cholesterol and ganglioside GM1 content of lipid rafts from the platelets of patients with AD might serve as a biochemical adjunct to the clinical diagnosis of AD.

Low Plasma Proportion of Omega 3-Polyunsaturated Fatty Acids Predicts Poor Outcome in Acute Non-Cardiogenic Ischemic Stroke Patients.

Background and PurposeAlterations in blood fatty acid (FA) composition are associated with cardiovascular diseases. We investigated whether plasma FA composition was related to stroke severity and functional outcome in acute ischemic stroke patients.MethodsWe prospectively enrolled 156 patients with first-episode cerebral infarction, within 7 days of symptom onset. The proportion of FAs was analyzed using gas chromatography, and the summation of the omega-3 polyunsaturated fatty acids (ω3-PUFA), 18:3 ω3 α-linolenic acid, 20:3 ω3 eicosatrienoic acid, 20:5 ω3 eicosapentaenoic acid (EPA), and 22:6 ω3 docosahexaenoic acid (DHA) was reported as Σω3-PUFAs. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. Poor functional outcome was defined by modified Rankin scale (mRS) ≥3 at three months after the index stroke.ResultsLower proportions of EPA (β=-0.751), DHA (β=-0.610), and Σω3-PUFAs (β=-0.462) were independently associated with higher NIHSS score, after adjusting for stroke subtype, hemoglobin, high density lipoprotein, high sensitivity C-reactive protein, fasting glucose, 16:0 palmitic acid, and Σsaturated fatty acids. Moreover, a lower proportion of DHA (odds ratio [OR]: 0.20, 95% confidence interval [CI]: 0.04-0.88), and Σω3-PUFAs (OR: 0.22, 95% CI: 0.05-0.84) showed an independent relationship with poor functional outcome after adjusting for age, sex, smoking status, NIHSS score, stroke subtype, and 16:0 palmitic acid.ConclusionsOur results demonstrate that ω3-PUFAs correlated with stroke severity on admission and functional outcomes at 3 months. ω3-PUFAs are potential blood biomarkers for prognosis of acute non-cardiogenic ischemic stroke patients.

Glucosylceramide and Lysophosphatidylcholines as Potential Blood Biomarkers for Drug-Induced Hepatic Phospholipidosis

Drug-induced phospholipidosis is one of the major concerns in drug development and clinical treatment. The present study involved the use of a nontargeting lipidomic analysis with liquid chromatography-mass spectrometry to explore noninvasive blood biomarkers for hepatic phospholipidosis from rat plasma. We used three tricyclic antidepressants (clomipramine [CPM], imipramine [IMI], and amitriptyline [AMT]) for the model of phospholipidosis in hepatocytes and ketoconazole (KC) for the model of phospholipidosis in cholangiocytes and administered treatment for 3 and 28 days each. Total plasma lipids were extracted and measured. Lipid molecules contributing to the separation of control and drug-treated rat plasma in a multivariate orthogonal partial least squares discriminant analysis were identified. Four lysophosphatidylcholines (LPCs) (16:1, 18:1, 18:2, and 20:4) and 42:1 hexosylceramide (HexCer) were identified as molecules separating control and drug-treated rats in all models of phospholipidosis in hepatocytes. In addition, 16:1, 18:2, and 20:4 LPCs and 42:1 HexCer were identified in a model of hepatic phospholipidosis in cholangiocytes, although LPCs were identified only in the case of 3-day treatment with KC. The levels of LPCs were decreased by drug-induced phospholipidosis, whereas those of 42:1 HexCer were increased. The increase in 42:1 HexCer was much higher in the case of IMI and AMT than in the case of CPM; moreover, the increase induced by IMI was dose-dependent. Structural characterization determining long-chain base and hexose delineated that 42:1 HexCer was d18:1/24:0 glucosylceramide (GluCer). In summary, our study demonstrated that d18:1/24:0 GluCer and LPCs are potential novel biomarkers for drug-induced hepatic phospholipidosis.

Metabolomic signatures in peripheral blood associated with Alzheimer's disease amyloid-β-induced neuroinflammation.

Discovery of biomarkers in peripheral blood is a crucial step toward the early diagnosis and repetitive monitoring of treatment response for Alzheimer's disease (AD). Metabolomics is a promising technology that can identify unbiased biomarkers. To explore potential blood biomarkers for AD via metabolic profiling with high-resolution magic angle spinning nuclear magnetic resonance techniques, we identified changes in peripheral blood metabolomic profiles in response to amyloid-β (Aβ)-induced neuroinflammation and co-treatment with gallate, a phytochemical known to have anti-neuroinflammatory properties. Alzheimer's-like (AL) model mice were produced by intracerebroventricular infusion of Aβ and compared with normal control mice with infusion of vehicle. AL mice were treated with either gallate (treated AL mice) or vehicle (untreated AL mice). Metabolomic analyses of both whole blood and plasma showed a clear separation between untreated AL mice and the other two groups, with levels of several metabolites involved in energy metabolism, including pyruvate and creatine, being significantly reduced in untreated AL mice compared with control and treated AL mice. Gallate treatment suppressed Aβ-induced overproduction of the inflammatory cytokine tumor necrosis factor-α in the hippocampus and normalized plasma levels of the affected metabolites. These results suggest that plasma levels of several metabolites could be indicative of both brain pathology and therapeutic responses, supporting the possibility of a close relationship between central neuroinflammation and systemic metabolic disturbance. These findings also suggest the potential of NMR-based metabolomics as a method to identify novel plasma biomarkers for AD, which could be confirmed by future translational research with human patients.

Gene expression profiling and putative biomarkers of calves 3 months after infection with Mycobacterium avium subspecies paratuberculosis

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease (JD), a chronic granulomatous intestinal inflammation of ruminants. Current diagnostic tools lack sensitivity to detect JD early in infection; therefore, alternatives are desired. The objective was to identify potential biomarkers in whole blood of high- and low-dose (LD) MAP-challenged Holstein-Friesian calves 3 months after inoculation. Infected calves were designated MAP-positive using the IFN-γ release assay. Differential expression of transcripts in whole blood was compared between non-infected controls and HD, as well as LD calves, using the Affymetrix® GeneChip® Bovine Genome Array. Microarray data were analyzed using RMA and PLIER algorithms; 296 transcripts were differentially expressed (17 had ≥1.5 fold change). The HD and LD calves had differential gene expression profiles for up to 80% of differentially expressed genes. Pathway analyses using Ingenuity Pathway Analysis (IPA®) indicated inhibition of several defence mechanisms, including apoptosis, leukocyte and lymphocyte trafficking, overall repression of gene expression and potentially hydrogen peroxide production in macrophages. Further validation using qPCR verified increased expression of CD46, ICOS, and CEP350, but decreased expression of CTLA4, YARS, and PARVB in infected calves. Additionally, a comparison of seropositive and seronegative infected calves identified transcripts predictive of seroconversion. We concluded that IL6ST/gp130 and CD22 may have important roles in the induction of antibodies against MAP. Putative biomarkers of early MAP infection with roles in immune responses were identified; in addition, the importance of infective dose on biomarkers was determined.

Proteomic biomarkers of recovered heart function

Chronic heart failure is a costly epidemic that affects up to 2% of people in developed countries. The purpose of this study was to discover novel blood proteomic biomarker signatures of recovered heart function that could lead to more effective heart failure patient management by both primary care and specialty physicians. The discovery cohort included 41 heart transplant patients and 20 healthy individuals. Plasma levels of 138 proteins were detected in at least 75% of these subjects by iTRAQ mass spectrometry. Eighteen proteins were identified that had (i) differential levels between pre-transplant patients with end-stage heart failure and healthy individuals; and (ii) levels that returned to normal by 1 month post-transplant in patients with stable heart function after transplantation. Seventeen of the 18 markers were validated by multiple reaction monitoring mass spectrometry in a cohort of 39 heart failure patients treated with drug therapy, of which 30 had recovered heart function and 9 had not. This 17-protein biomarker panel had 93% sensitivity and 89% specificity, while the RAMP® NT-proBNP assay had the same specificity but 80% sensitivity. Performance further improved when the panel was combined with NT-proBNP, yielding a net reclassification index relative to NT-proBNP of 0.28. We have identified potential blood biomarkers of recovered heart function by harnessing data from transplant patients. These biomarkers can lead to the development of an inexpensive protein-based blood test that could be used by physicians to monitor response to therapy in heart failure, resulting in more personalized, front-line heart failure patient management.

Comparison of serum, EDTA plasma and P100 plasma for luminex-based biomarker multiplex assays in patients with chronic obstructive pulmonary disease in the SPIROMICS study

BackgroundAs a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression. To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100™).Methods105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects. The reliability coefficient and the coefficient of variation (CV) were calculated. The performance of each analyte and mean analyte levels were evaluated across sample types.Results20% of analytes were not consistently detectable in any sample type. Higher reliability and/or smaller CV were determined for 12 analytes in EDTA plasma compared to serum, and for 11 analytes in serum compared to EDTA plasma. While reliability measures were similar for EDTA plasma and P100 plasma for a majority of analytes, CV was modestly increased in P100 plasma for eight analytes. Each analyte within a multiplex produced independent measurement characteristics, complicating selection of sample type for individual multiplexes.ConclusionsThere were notable detectability and measurability differences between serum and plasma. Multiplexing may not be ideal if large reliability differences exist across analytes measured within the multiplex, especially if values differ based on sample type. For some analytes, the large CV should be considered during experimental design, and the use of duplicate and/or triplicate samples may be necessary. These results should prove useful for studies evaluating selection of samples for evaluation of potential blood biomarkers.

Evaluation of Current and New Biomarkers in Severe Preeclampsia: A Microarray Approach Reveals the VSIG4 Gene as a Potential Blood Biomarker

Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C), endothelial activation (such as soluble endoglin and CD146), and the release of total and platelet-derived microparticles. These markers enabled us to discriminate the preeclampsia condition from a normal pregnancy but were not sufficient to distinguish severe from non-severe preeclampsia. We then used a microarray to study the transcriptional signature of blood samples. Preeclampsia patients exhibited a specific transcriptional program distinct from that of the control group of women. Interestingly, we also identified a severity-related transcriptional signature. Functional annotation of the upmodulated signature in severe preeclampsia highlighted two main functions related to “ribosome” and “complement”. Finally, we identified 8 genes that were specifically upmodulated in severe preeclampsia compared with non-severe preeclampsia and the normotensive controls. Among these genes, we identified VSIG4 as a potential diagnostic marker of severe preeclampsia. The determination of this gene may improve the prognostic assessment of severe preeclampsia.

Correlation of Adrenomedullin gene expression in peripheral blood leukocytes with severity of ischemic stroke

Human adrenomedullin (ADM), a 52-amino acid peptide, belongs to the calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. ADM acts as a multifunctional regulatory peptide and is upregulated in response to hypoxia. Previous microarray studies have found increased ADM gene (ADM) expression in peripheral blood cells of patients with stroke, however, it is unknown if an increased ADM level is correlated with severity of human ischemic stroke. This study investigated ADM expression in peripheral blood leukocytes (PBL) of healthy controls and subjects at day 1, week 1 and week 3 postacute ischemic stroke using rtPCR methodology. We found that ADM expression was significantly upregulated on the first day of stroke compared to the healthy subjects and the disease controls; the levels remained elevated for up to week 3. Further, ADM expression at day 1 was correlated with stroke severity measured by the National Institute of Healthy Stroke Scale (NIHSS), the modified Barthel Index (mBI) and the modified Rankin Scale (mRS). This could indicate that ADM expression level is related to the severity of tissue damage. We suggest that increased ADM expression in PBL after acute ischemic stroke is most likely to indicate that these cells have been subjected to hypoxia and that the magnitude of expression is likely to be related to the volume of hypoxic tissue. Hypoxia can affect lymphocytes function and could affect the immune response to stroke. The correlation of ADM expression level with the measures of stroke severity implicates ADM –a potential blood bio-marker in studies of ischemic stroke.

Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients

Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Using a case-control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke. We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial.

Potentiality of a triple microRNA classifier: miR-193a-3p, miR-23a and miR-338-5p for early detection of colorectal cancer

BackgroundMicroRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs offer great potential as cancer biomarkers. The objective of this study was to correlate the differential expression of miRNAs in tissue and blood in the identification of biomarkers for early detection of colorectal cancer (CRC).MethodsThe study was divided into two phases: (I) Marker discovery by miRNA microarray using paired cancer tissues (n?=?30) and blood samples (CRC, n?=?42; control, n?=?18). (II) Marker validation by stem-loop reverse transcription real time PCR using an independent set of paired cancer tissues (n?=?30) and blood samples (CRC, n?=?70; control, n?=?32). Correlation analysis was determined by Pearson’s test. Logistic regression and receiver operating characteristics curve analyses were applied to obtain diagnostic utility of the miRNAs.ResultsSeven miRNAs (miR-150, miR-193a-3p, miR-23a, miR-23b, miR-338-5p, miR-342-3p and miR-483-3p) have been found to be differentially expressed in both tissue and blood samples. Significant positive correlations were observed in the tissue and blood levels of miR-193a-3p, miR-23a and miR-338-5p. Moreover, increased expressions of these miRNAs were detected in the more advanced stages. MiR-193a-3p, miR-23a and miR-338-5p were demonstrated as a classifier for CRC detection, yielding a receiver operating characteristic curve area of 0.887 (80.0% sensitivity, 84.4% specificity and 83.3% accuracy).ConclusionDysregulations in circulating blood miRNAs are reflective of those in colorectal tissues. The triple miRNA classifier of miR-193a-3p, miR-23a and miR-338-5p appears to be a potential blood biomarker for early detection of CRC.

A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2gene carriers

BackgroundBreast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers.Methods/designParticipants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants.DiscussionThe results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive of breast cancer occurrence.

Cocktail Blood Biomarkers: Prediction of Clinical Outcomes in Patients with Acute Ischemic Stroke

Background: Timely prediction of stroke outcomes is important for proper personalized treatment. In the present study, we aimed to develop cocktail blood biomarkers to increase prediction efficiency using a combination of hemostasis, inflammatory and repair-related biomarkers. Methods: 105 patients suffering from acute ischemic stroke were divided into good outcome group and poor outcome group by modified Rankin Scale (mRS). Cytokines including CD40L, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-17 and TNF-α, as well as hemostasis markers fibrinogen, fibrin degradation products (FDP), D-dimer, tissue plasminogen activator, and plasminogen activation inhibitor-1 in plasma were examined by ELISA. Repair-related biomarker microRNA-210 (miR-210) was measured by real-time PCR. The prediction efficiency was explored by receiver operator characteristic analysis. Results: We demonstrated that FDP, IL-6 and miR-210 levels were closely associated with mRS in stroke patients. The prediction sensitivity of FDP, IL-6 and miR-210 for stroke outcome was 72.0, 86.7 and 82.5%, respectively. Using a combination of biomarkers including FDP, IL-6 and miR-210, the prognostic sensitivity of ischemic stroke increased to 95.2%. Conclusion: The combination of FDP, IL-6 and miR-210 has a high sensitivity for predicting stroke recovery, it serves as a potential cocktail blood biomarker. It provides a novel approach for stroke prognosis.

Biomarkers for acute GVHD: can we predict the unpredictable?

Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-α, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3α, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized.

Potential blood biomarkers for stroke

Stroke is one of the most common causes of death worldwide and a major cause of acquired disability in adults. Despite advances in research during the last decade, prevention and treatment strategies still suffer from significant limitations, and therefore new theoretical and technical approaches are required. Technological advances in the proteomic and metabolomic areas, during recent years, have permitted a more effective search for novel biomarkers and therapeutic targets that may allow for effective risk stratification and early diagnosis with subsequent rapid treatment. This review provides a comprehensive overview of the latest candidate proteins and metabolites proposed as new potential biomarkers in stroke.