Brain injury after intracranial hemorrhage (ICH) results in significant morbidity and mortality. Blood brain barrier (BBB) disruption is a hallmark of ICH-induced brain injury; however, data mirroring BBB disruption in human ICH are scarce. The aim of this study was to assess the significance of circulating biomarkers in evaluating BBB disruption after ICH. Twenty-two patients with ICH were recruited in this study. Concentrations of the tight junction proteins (TJs) Claudin-5 (CLDN5), Occludin (OCLN), and zonula occludens 1 (ZO-1) and vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were measured by using enzyme-linked immunosorbent assay in serum and cerebrospinal fluid (CSF) samples obtained from patients with ICH. The white blood cell (WBC) count in blood and CSF, albumin (ALB) levels in the CSF (ALBCSF), and the BBB ratio were significantly higher in the ICH than in controls (p < 0.05). Significantly higher levels of CLDN5, OCLN, ZO-1, MMP-9, and VEGF in CSF were observed in the ICH group; these biomarkers were also positively associated with BBB ratio (p < 0.05). Our data revealed that circulating TJs could be considered the potential biomarkers reflecting the integrity of the BBB in ICH.

MicroRNA (miRNA), which has been shown to correlate with liver functions, has been proposed as a new biomarker reflecting liver injury. The aim of the study was to investigate miRNA-122 (miR-122) and mir-RNA-199a (miR-199a) as a biomarker for predicting therapeutic efficacy in hepatitis C (HepC) patients. A total of 47 HepC 1b patients and 16 healthy subjects were enrolled in the study. Serum and exosomal mir-RNAs and other conventional biomarkers reflecting liver function were evaluated. The miR-122 levels in serum (miR-122 ) and exosomes (miR-122 ) were significantly lower in the Hepatitis C virus (HCV) genotype 1b patients than in the normal controls, but these levels were higher compared to the non-genotype 1b group. The mean miR-122 level in the sustained virological response (SVR) group was significantly higher than that in the non-response (NR) group (P < 0.01), and the miR-122 level in the SVR group was also higher than that in the NR group (P > 0.05), although this difference was not significant. miR-199a levels showed similar trends with the miR-122 levels in serum and exosomes. HCV RNA was negatively correlated with the miR-122 (r = -0.473, P = 0.004) and miR-122 (r = -0.424, P = 0.009) levels. miR-122 levels were positively associated with miR-199a levels (r = 0.453, P = 0.002) Univariate and multivariate regression analyses reveal that the miR-122 levels and ALT/AST ratio demonstrated a predictive value in evaluating patient outcomes. Serum miR-122 and miR-199a are potential biomarkers that reflect therapeutic efficacy.

Metastasis to the central nervous system (CNS) is the primary obstacle in leukemia treatment. Matrix metalloproteinase-9 (MMP-9), chemokine ligand-2 (CCL2) and soluble vascular adhesion molecule-1 (sVCAM-1) play crucial roles in tumor cell adhesion, motivation and survival, but their roles in leukemia CNS metastasis remain to be elucidated. We investigated the prognostic significance of serum and cerebrospinal fluid (CSF) MMP-9, CCL2 and sVCAM-1 in leukemia patients to explore their potential as predictive biomarkers of the development of CNS leukemia (CNSL). MMP-9, CCL2 and sVCAM-1 were measured in paired CSF and serum samples collecting from 33 leukemia patients with or without CNS metastasis. Other risk factors related to CNSL prognosis were also analyzed. sVCAM-1Serum and CCL2Serum/CSF were significantly higher in the CNSL group than in the non-CNSL group and the controls (p < 0.05). MMP-9Serum was insignificantly lower in the CNSL group than in the non-CNSL group and the controls (p > 0.05). No differences were found for the sVCAM-1Serum, CCL2Serum, and MMP-9Serum levels between non-CNSL patients and controls (p > 0.05). MMP-9CSF was significantly higher in the CNSL group than both the non-CNSL and the control groups (p < 0.05). The indexes of sVCAM-1, CCL2, and MMP-9 in the CNSL group were lower than in the controls (p < 0.05). Positive correlations were determined between the MMP-9CSF and the ALBCSF/BBB value/WBCCSF, between sVCAM-1Serum and the WBCCSF/BBB value. Negative correlations existed between MMP-9Serum and the ALBCSF/BBB value/WBCCSF, and between the CCL2 index and ALBCSF. sVCAM-1Serum was positively associated with event-free survival (EFS), and patients with higher levels of ALBCSF, MMP-9CSF/Serum, CCL2CSF/Serum, and sVCAM-1CSF/Serum had shorter EFS. MMP-9CSF, CCL2CSF and sVCAM-1CSF are the first three principal components analyzed by cluster and principal component analysis. Our data suggest that MMP-9, CCL2 and sVCAM-1 in the CSF may be more potent than serum in predicting the possibility of leukemia metastatic CNS and the outcome of CNSL patients.

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