Prognostic Value of Plasma Visfatin Level for Chinese Patients with Severe Carbon Monoxide Poisoning.

BACKGROUND: This prospective observatory study was designed to investigate whether plasma visfatin might serve as a marker of prognosis in patients with severe carbon monoxide (CO) poisoning. METHODS: A total of 52 consecutive patients with severe CO poisoning and 52 gender- and age- matched healthy subjects were enrolled in the study, and their plasma visfatin levels were determined using an enzyme-linked immunosorbent assay. The clinical outcomes, including in-hospital mortality, 6-month mortality, and poor outcome (Glasgow Outcome Scale score of 1 - 3), were recorded. RESULTS: Plasma visfatin levels were statistically significantly higher in patients than in healthy controls (97.4 ± 28.0 ng/mL vs. 12.1 ± 3.7 ng/mL; p < 0.001). Multivariate logistic regression analysis showed that plasma visfatin level was an independent prognostic predictor of in-hospital mortality [odds ratio (OR), 1.214; 95% confidence interval (CI), 1.103 - 1.425; p < 0.001], 6-month mortality (OR, 1.269; 95% CI, 1.085 - 1.534; p < 0.001), and 6-month poor outcome (OR, 1.302; 95% CI, 1.023 - 1.520; p < 0.001). Moreover, receiver operating characteristic curves showed that plasma visfatin level had high predictive value for in-hospital mortality [area under curve (AUC), 0.931; 95% CI, 0.832 - 1.000], 6-month mortality (AUC, 0.894; 95% CI, 0.801 - 0.987), and 6-month poor outcome (AUC, 0.886; 95% CI, 0.796 - 0.977). CONCLUSIONS: Plasma visfatin levels are significantly higher in patients with severe CO poisoning and could be a useful biomarker to predict short- and long-term clinical outcome after severe CO poisoning.

Neuroprotective effects of erythropoietin in patients with carbon monoxide poisoning.

The purpose of this study was to evaluate the efficacy of erythropoietin (EPO) for treating patients with carbon monoxide (CO) poisoning. We conducted a randomized, prospective study of 103 patients with CO poisoning in two groups: an EPO group (n = 54; patients received EPO) and a placebo group (n = 49; patients received normal saline). The study endpoints were the functional outcome at day 30 (the Barthel index and neurologic sequelae), National Institutes of Health Stroke Scale (NIHSS) score, and the levels of S-100ß. At 18 days, the NIHSS score improved significantly and S-100ß levels significantly decreased in patients in the EPO group. At 30 days, patients in the EPO group had a superior Barthel index and fewer patients had delayed neurologic sequelae (DNS). This study demonstrated that early administration of EPO to patients with CO poisoning improved neurological outcomes and reduced the incidence of DNS.

Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes.

Breast cancer is one of the main types of cancer affecting the health of females worldwide. Despite improvements in therapeutic approaches, cancer patients succumb to the disease due to metastasis itself, rather than the primary tumor from which metastases arise, emphasizing the need for the better understanding of the biological bases that contribute to disease progression. RAB22A, a member of the proto-oncogene RAS family, plays an important role in the formation, trafficking and metabolism of exosomes, and is associated with the occurrence and development of multiple human cancers. In this study, we demonstrate that the upregulation of RAB22A is associated with breast cancer progression and lymph node metastasis. We identified a signature of RAB22A and miR-193b that exhibited a negative association in metastatic as opposed to the surrounding normal cells, and RAB22A was identified as the target gene of miR-193b. While RAB22A was found to regulate exosomes-mediated breast cancer cell proliferation, invasion and migration, these biological characteristics were diminished in the breast cancer cells in which the RAB22A gene was knocked down or in the cells in which the exosomes were dissolved by proteinase K/RNase treatment. On the whole, the findings of this study demonstrate the critical role that miR-193b plays in the regulation of RAB22A-mediated exosome function during cancer growth and metastasis, which may have significant implications on cancer therapy.

Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients.

BACKGROUND: Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. OBJECTIVE: The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. METHODS: Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). RESULTS: Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. CONCLUSION: Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.

Erythropoietin Protects Rat Brain Injury from Carbon Monoxide Poisoning by Inhibiting Toll-Like Receptor 4/NF-kappa B-Dependent Inflammatory Responses.

Inflammatory responses play critical roles in carbon monoxide (CO) poisoning-induced cerebral injury. The present study investigated whether erythropoietin (EPO) modulates the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) inflammatory signaling pathways in brain injury after acute CO poisoning. EPO (2500 and 5000 U/kg) was injected subcutaneously twice a day after acute CO poisoning for 2 days. At 48 h after treatment, the expression levels of TLR4 and NF-κB as well as the levels of inflammatory cytokines in the hippocampal tissues were measured. Our results showed that CO poisoning induced a significant upregulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat hippocampal tissues. Treatment with EPO remarkably suppressed the gene and protein expression levels of TLR4 and NF-κB, as well as the concentrations of TNF-α, IL-1ß, and IL-6 in the hippocampal tissues. EPO treatment ameliorated CO poisoning-induced histological edema and neuronal necrosis. These results suggested that EPO protected against CO poisoning-induced brain damage by inhibiting the TLR4-NF-κB inflammatory signaling pathway.

Effect of vasopressin on hippocampal injury in a rodent model of asphyxial cardiopulmonary arrest.

The effect of vasopressin on the neuronal injury following the restoration of spontaneous circulation (ROSC) in cardiac arrest (CA) is not yet fully understood. The present study was conducted in order to investigate the effect of vasopressin alone, or in combination with epinephrine, on the ROSC and hippocampal injury in a rat model of asphyxial CA. Asphyxial CA was induced in 144 rats by clamping the tracheal tube, and animals were allocated equally into the following three groups: Treatment with vasopressin (0.8 U/kg); epinephrine (0.2 mg/kg); or vasopressin (0.8 U/kg) plus epinephrine (0.2 mg/kg). An additional 48 rats underwent a sham surgical procedure without asphyxial CA and cardiopulmonary resuscitation. Hippocampal tissue was harvested at 1, 3, 6 and 12 h post-ROSC, and the levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 were determined using immunohistochemistry. In comparison with rats treated with epinephrine alone, higher ROSC success rates were observed in rats treated with vasopressin, or vasopressin plus epinephrine. In addition, treatment with vasopressin attenuated hippocampal injury and reduced hippocampal p38 MAPK and NF-κB expression more efficiently compared with epinephrine alone. In conclusion, treatment with vasopressin exhibits a protective effect in patients experiencing CA, and this may be attributed to the inhibition of p38 MAPK and NF-κB expression.

Plasma copeptin as a predictor of intoxication severity and delayed neurological sequelae in acute carbon monoxide poisoning.

The present study was designed to assess the usefulness of measuring plasma levels of copeptin (a peptide co-released with the hypothalamic stress hormone vasopressin) as a biomarker for the severity of carbon monoxide (CO) poisoning and for predicting delayed neurological sequelae (DNS). Seventy-two patients with CO poisoning and 72 sex and age matched healthy individuals were recruited. Plasma copeptin levels were measured on admission from CO poisoning patients and for healthy individuals at study entry by using a sandwich immunoassay. The CO poisoning patients were divided into two groups according to severity (unconscious and conscious) and occurrence of DNS. The mean plasma copeptin levels (52.5±18.5 pmol/L) in the unconscious group were significantly higher than in the conscious group (26.3±12.7 pmol/L) (P<0.001). Plasma copeptin levels of more than 39.0 pmol/L detected CO poisoning with severe neurological symptoms e.g. unconsciousness (sensitivity 84.6% and specificity 81.4%). The plasma copeptin levels were higher in patients with DNS compared to patients without DNS (52.2±20.6 pmol/L vs. 27.9±14.8 pmol/L, P<0.001). Plasma copeptin levels higher than 40.5 pmol/L predicted the development of DNS (sensitivity 77.8%, specificity 82.1%). Plasma copeptin levels were identified as an independent predictor for intoxication severity [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112-1.638, P=0.002] and DNS (OR 1.313, 95% CI 1.106-1.859, P=0.001). Thus, plasma copeptin levels independently related to intoxication severity and were identified as a novel biomarker for predicting DNS after acute CO poisoning.

Elevated serum ubiquitin C-terminal hydrolase-L1 levels in patients with carbon monoxide poisoning.

OBJECTIVE: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been established as a reliable and potential biomarker of neuronal damage after acute neurologic insults, such as ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. However, the effect of serum UCH-L1 levels has not been investigated in carbon monoxide (CO)-poisoned patients. The aim of the present study was to evaluate whether serum UCH-L1 levels are a reliable marker of brain damage and the association of UCH-L1 with outcome. DESIGN AND METHODS: This case-control study enrolled 46 CO-poisoned subjects and 30 controls. Using an enzyme-linked immunosorbent assay (ELISA) kit, we studied the temporal profile of serum UCH-L1 levels at 6, 12, 24 and 48 h after acute CO poisoning. Poisoning severity was assessed using the Glasgow Coma Scale (GCS) score. Long-term outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months after poisoning. RESULTS: Compared with controls, CO-poisoned patients had significantly elevated serum levels of UCH-L1 at each time point after poisoning. There were significantly higher levels of UCH-L1 in CO-poisoned patients with a lower GCS score as well as in those with a poor 6-month outcome dichotomized GOS. CONCLUSIONS: Serum levels of UCH-L1 appear to have potential clinical utility in providing valuable information about poisoning severity and outcome after CO poisoning.