Search

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.

Context Metabolic disorders, especially dysregulated lipid metabolism, increase the risk of cardiovascular mortality in acromegaly. Previous studies measuring plasma macromolecular lipids have yielded conflicting results. Purpose To explore the plasma lipid metabolite profiles by metabolomics analysis and identify potential metabolites associated with cardiac function in acromegaly. Methods Plasma was obtained from 80 newly diagnosed, untreated patients with acromegaly and 80 healthy controls. Echocardiography was performed. Based on the results of an oral glucose tolerance test (OGTT), patients were categorized into 2 groups: normal glucose tolerance (NGT, n = 28) and impaired glucose tolerance or diabetes mellitus (IGT/DM, n = 52). High-performance liquid chromatography–mass spectrometry (HPLC–MS)-based metabolomics analysis was conducted. Data were processed by principal components analysis (PCA), orthogonal partial least square-discriminant analysis (OPLS-DA), and MetaboAnalyst 4.0. Associations between metabolic substances and cardiovascular parameters were also explored. Results Metabolomics uncovered a distinct metabolic pattern between acromegaly and healthy controls, and perturbed pathways mainly include glycerophospholipid metabolism, sphingolipid metabolism, as well as linoleic acid metabolism. Collective analysis showed that phosphatidylethanolamine (PE) (22:6/16:0) was positively correlated with LV mass, while lysophosphatidylcholine (LysoPC) (16:0) was positively correlated with fractional shortening (FS) and left ventricle ejection fraction (LVEF). Conclusion Patients with acromegaly have distinct lipid metabolite profiling, while PE (22:6/16:0) and LysoPC (16:0) are correlated with cardiac structure and function, which may contribute to the risk of cardiovascular complications.

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.

Objective Delayed cerebral ischemia (DCI) greatly contributes to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. Expression of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1) was substantially raised in the basilar arterial wall of SAH rabbits. We attempted to ascertain the relationship between serum soluble LOX‐1 (sLOX‐1) levels and the occurrence of DCI after aSAH. Materials and methods We enrolled 125 aSAH patients and 125 healthy controls. Serum sLOX‐1 levels were quantified using commercial enzyme‐linked immunosorbent assay kit. The relationship between sLOX‐1 levels and DCI was analyzed utilizing the multivariate logistic regression analysis. Results Serum sLOX‐1 levels were significantly higher in stroke patients than in controls (median: 1,450.2 vs. 445.7 pg/ml, p 1,450.2 pg/ml, WFNS scores and modified Fisher scores were the independent predictors of DCI. Under receiver operating characteristic curve, serum sLOX‐1 levels exhibited a significant discriminatory capability (area under curve 0.825, 95% confidence interval 0.747–0.887). The predictive power of serum sLOX‐1 levels was similar to those of WFNS scores and modified Fisher grade (both p > .05). Moreover, serum sLOX‐1 levels significantly improved their predictive capability (both p, There is a substantial elevation in serum sLOX‐1 levels after aSAH. There is an intimate correlation of serum sLOX‐1 levels with hemorrhagic severity. There is an independent association of serum sLOX‐1 levels with delayed cerebral ischemia.

Objective Vitronectin is an extracellular matrix protein, the synthesis of which by glioma cells correlates with tumor grade. The current study was designed to investigate the relationship between serum vitronectin levels and clinicopathological characteristics, diagnosis and prognosis in glioma patients. Methods In a prospective observatory study, a total of 98 glioma patients, 98 healthy controls, 98 other non-glioma brain tumors, and 98 other non-tumor neurological diseases were recruited. Following univariate analyses, multivariate analyses were performed to explore the associations of serum vitronectin levels with survival and clinicopathological parameters. Receiver operating characteristic curve analysis was done to assess its diagnostic and prognostic predictive value. Results Serum vitronectin levels were significantly elevated in glioma patients as compared with other groups. High Wealth Health Organization grade was independently associated with high vitronectin levels. Serum vitronectin levels could significantly distinguish glioma patients from other groups and discriminate high-grade glioma from low-grade glioma. Vitronectin levels markedly predicted 5-year progression and 5-year mortality. Moreover, serum vitronectin was identified as an independent predictor for 5-year overall survival and 5-year progression-free survival as well as 5-year mortality and 5-year progression. Conclusion Serum vitronectin may be a promising diagnostic and prognostic biomarker that can be detected in the peripheral blood of patients with glioma.

Notch signaling is a highly conserved pathway that regulates cell fate decisions during embryonic development. Notch activation endangers neurons by modulating NF-κB and HIF-1α pathways, however, the role of Notch signaling in activating JNK/c-Jun following intracerebral hemorrhage (ICH) has not been investigated. In this study, we used rat ICH models and thrombin-induced cell models to investigate the potential role of Notch-1/JNK signals. Our findings revealed that Notch-1 and JNK increased in hematoma-surrounding neurons tissues following ICH during ischemic conditions (all p

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.

Background Increased circulating soluble CD40 ligand (sCD40L) levels have been reported to be associated with severity and mortality of severe traumatic brain injury. The current study tested the hypothesis that elevated plasma sCD40L levels are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). Methods Plasma sCD40L concentrations of 120 aSAH patients and 120 healthy volunteers were measured using enzyme-linked immunosorbent assay. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. Results Plasma sCD40L levels were significantly elevated in aSAH patients compared with healthy controls; plasma sCD40L levels were highly associated with clinical severity reflected by World Federation of Neurological Surgeons (WFNS) score and Fisher score; sCD40L emerged as an independent predictor of 6-month mortality and unfavorable outcome and 6-month overall survival; although a combined logistic-regression model did not demonstrate the additive benefit of sCD40L to WFNS score and Fisher score, sCD40L possessed similar predictive value to WFNS score and Fisher score based on receiver operating characteristic curves. Conclusions Higher plasma sCD40L levels on presentation are associated with clinical severity and have potential to be a good prognostic biomarker of aSAH.

Increased plasma adrenomedullin levels have been reported in critically ill patients. This study tested the hypothesis that plasma adrenomedullin levels are significantly increased in patients with acute spontaneous aneurysmal subarachnoid hemorrhage, and are predictive of clinical outcomes. Plasma adrenomedullin levels from 120 adult patients with spontaneous aneurysmal subarachnoid hemorrhage and 120 healthy volunteers during the study period were evaluated. Mortality and poor long-term outcome (Glasgow Outcome Scale score of 1-3) at 6 months were recorded. Data showed that circulating plasma adrenomedullin levels significantly increased in patients on admission compared with the volunteers. In patients who died or had poor outcome at 6 months, plasma adrenomedullin levels were significantly higher compared with survivors and patients with good outcome. Plasma adrenomedullin levels on presentation were highly associated with clinical severity assessed using World Federation of Neurological Surgeons score and Fisher score, emerged as the independent risk factor of 6-month mortality and poor outcome, and possessed similar predictive value to World Federation of Neurological Surgeons score and Fisher score based on receiver operating characteristic curves. A combined logistic-regression model did not demonstrate the additive benefit of adrenomedullin to World Federation of Neurological Surgeons score and Fisher score. Thus, higher plasma adrenomedullin levels on presentation are associated with clinical severity and worse outcomes in patients with acute spontaneous aneurysmal subarachnoid hemorrhage.