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Cerebrocardiac syndrome (CCS) is a common complication after severe traumatic brain injury (sTBI) and its occurrence obviously increases the risk of a poor outcome. Macrophage migration inhibitory factor (MIF) acts as an inflammatory cytokine and its circulating concentration are related to acute heart and brain injury. The aim of this study was to examine the association of serum concentration of MIF with posttraumatic CCS.From January 2016 to February 2019, 116 sTBI patients and 116 healthy controls with similar age and gender percentage were recruited. Relationship between serum MIF concentration and CCS was assessed using multivariate analysis.Serum MIF concentration of patients were significantly higher than those among controls. Serum MIF concentration were intimately correlated with Glasgow coma scale scores (t = -5.553, P 0.001) and serum C-reactive protein concentration (t = 5.320, P 0.001) in a multivariate linear regression model. 61 patients (52.6%) displayed CCS. Under ROC curve analylsis, there was a strong discriminatory ability for CCS regarding serum MIF concentration (area under curve, 0.834; 95% confidence interval, 0.754-0.897). Serum MIF concentration were highly associated with CCS independent of other confounding factors (odds ratio, 5.608; 95% CI: 1.896-16.587).Increased MIF in serum may be a useful biomarker for early detection of CCS after head trauma.

Background Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) might contribute to brain inflammation after acute brain injury. The current study was designed to investigate whether serum soluble TWEAK (sTWEAK) can serve as a potential biomarker for functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). Methods In this single-center prospective, observational study, admission serum sTWEAK concentrations were quantified among 112 aSAH patients. Impact of serum sTWEAK concentrations on a poor outcome (Glasgow outcome scale score 1–3) at 6 months after stroke onset was determined using multivariate analysis. Results Admission serum sTWEAK concentrations were intimately correlated with serum C-reactive protein concentrations, World Federation of Neurological Surgeons scores and modified Fisher scores. A total of 38 patients (33.9%) had a poor outcome at post-hemorrhagic 6 months. Admission serum sTWEAK concentrations were substantially higher in patients with a poor outcome than in the other remainders. Under receiver operating characteristic curve, serum sTWEAK concentrations significantly distinguished a poor outcome. Serum sTWEAK concentrations > 3.23 ng/ml discriminated the risk of a poor outcome with medium-high sensitivity and specificity and independently predicted a poor outcome. Conclusions Serum sTWEAK, in close correlation with inflammation and hemorrhagic severity, might represent a potential biomarker for predicting clinical outcome after aSAH.

Background Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA. Methods The expression of BRD4 was detected in NFPA, GHPA, and normal pituitary tissues. The efficacies of BRD4 inhibitors were evaluated in GH3 and MMQ cell lines, patient-derived tumor cells, and in vivo mouse xenograft models of PA. Standard western blots, real-time PCR, and flow cytometry experiments were performed to investigate the effect of BRD4 inhibitors on cell cycle progression, apoptosis, and the expression patterns of downstream genes. Results Immunohistochemistry studies demonstrated the overexpression of BRD4 in NFPA and GHPA. In vitro and in vivo studies showed that treatment with the BRD4 inhibitor ZBC-260 significantly inhibited the proliferation of PA cells. Further mechanistic studies revealed that ZBC-260 could downregulate the expression of c-Myc, B-cell lymphoma 2 (Bcl2), and related genes, which are vital factors in pituitary tumorigenesis. Conclusion In this study, we determined the overexpression of BRD4 in NFPA and GHPA and assessed the effects of BRD4 inhibitors on PA cells in vitro and in vivo. Our findings suggest that BRD4 is a promising therapeutic target for NFPA and GHPA.

Oxidized low-density lipoprotein (ox-LDL) and its receptor, lectin-like ox-LDL receptor-1 (LOX-1) are involved in the pathogenesis of atherosclerosis. Expression of LOX-1 was substantially raised in the basilar arterial wall of subarachnoid hemorrhage (SAH) rabbits. We ascertained the relationship between serum soluble LOX-1 concentrations and functional outcome after human aneurysmal SAH.We enrolled 94 aneurysmal SAH patients and 94 healthy controls. Serum soluble TOX-1 concentrations were quantified using commercial enzyme-linked immunosorbent assay kit. A poor outcome was defined as Glasgow outcome scale score of 1-3.Median values of serum soluble LOX-1 in stroke patients were significantly higher than those in controls (1.5 vs. 0.4 ng/ml, P 0.001). Thirty patients (31.9%) had a poor outcome at 6 months after stroke. Serum soluble LOX-1 was a strong predictor of poor outcome (OR 5.20, 95% CI 1.25-22.04). Serum soluble LOX-1 concentrations exhibited a significant discriminatory capability (area under curve 0.811, 95% confidence interval 0.717-0.884). The predictive powers of World Federation of Neurological Surgeons grade, Hunt-Hess grade, modified Fisher grade, and serum soluble LOX-1 concentrations were comparable (all P 0.05).Serum soluble LOX-1 appears to have the potential to become a promising prognostic predictor after human aneurysmal SAH.

Background Intracerebral hemorrhage (ICH) pathophysiology involves inflammation. Macrophage migration inhibition factor (MIF), a pro-inflammatory cytokine, is related to prognosis of ischemic stroke. The aim of this study was to investigate whether serum MIF levels are associated with severity and outcomes in patients with acute ICH. Methods We enrolled a total of 120 consecutive ICH patients and 120 healthy controls and sampled blood on admission and at study entry respectively. Enzyme-linked immunosorbent assay was used to quantify serum MIF levels. Results Serum MIF levels were higher in patients compared with controls and correlated with hematoma volume, National Institutes of Health Stroke Scale (NIHSS) scores and plasma C-reactive protein levels. After adjusting for other significant outcome predictors, MIF in serum was an independent predictor of 6-month overall survival and unfavorable outcome (modified Rankin Scale score > 2). Areas under receiver-operating characteristic curve (ROC) of serum MIF levels, hematoma volume and NIHSS scores were similar for 6-month unfavorable outcome. Moreover, serum MIF levels significantly improved areas under ROC of hematoma volume and NIHSS scores. Conclusions MIF in serum might be a potential biomarker for reflecting inflammation, severity and prognosis of ICH patients.

Circulating levels of thioredoxin (Trx), a potent anti-oxidant that modulates inflammation, cell growth and apoptosis, are increased in various critical care conditions. The purpose of this study was to establish the relationship between serum Trx levels and prognosis of aneurysmal subarachnoid hemorrhage (aSAH).An enzyme-linked immunosorbent assay measurement of Trx was performed in serum from 132 patients and 132 healthy volunteers. Clinical outcomes included 6-month mortality and unfavorable outcome (Glasgow outcome scale score of 1-3).The serum Trx levels were significantly higher in patients than in controls (23.4±12.2 ng/mL vs.8.5±4.0 ng/mL, P0.001) and had close relation to the World Federation of Neurological Surgeons (WFNS) scores (r=0.461, P0.001) and modified Fisher scores (r=0.459, P0.001). Trx was an independent predictor for 6-month mortality (Odds ratio, 1.386; 95% confidence interval, 1.015-2.161; P0.001) and 6-month unfavorable outcome (Odds ratio, 1.297; 95% confidence interval, 1.012-2.002; P0.001). Based on receiver operating characteristic curve, TRX had similar prognostic value compared with WFNS scores and modified Fisher scores and also significantly improved their prognostic value for 6-month unfavorable outcome, but not for 6-month mortality.Elevated plasma Trx levels are correlated with the severity and poor prognosis, substantializing Trx as a potential prognostic predictive biomarker following aSAH.