Androgen is responsible for enhanced susceptibility of melatonin against traumatic brain injury in females.

BACKGROUND: Numerous publications have demonstrated that melatonin administration is associated with mortality reduction and improvement in neurological outcomes after traumatic brain injury (TBI). However, there are significant sex differences in several diseases associated with melatonin. We aimed to determine whether androgen was responsible for enhanced susceptibility of melatonin against TBI in females, as well as potential molecular mechanisms. METHODS: Weight-drop was used to establish a rodent model of TBI. Melatonin (10 mg/kg) and testosterone (1 mg/kg) were administered three times every day for three days after TBI using subcutaneous injection, respectively. Seven days after TBI, an open field assay was used to evaluate locomotor and exploratory activities. Neuronal amount, neuronal apoptosis, and expression of phosphorylated extracellularly regulated protein kinases 1/2 (ERK1/2), c-jun N-terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (p38MAPK) in neurons were assessed using immunofluorescence assay seven days after TBI. The expression of caspase-3, Bax, and Bcl-2 in the frontal cortex was detected using western blot. RESULTS: Compared with female rats, melatonin administration exhibited more neuroprotective effects (including improved locomotor and exploratory activities, elevated neuronal amount, and reduced neuronal apoptosis) in male rats exposed to TBI. Moreover, testosterone significantly improved locomotor and exploratory activities, elevated neuronal amount, decreased neuronal apoptosis, downregulated phosphorylation of JNK1/2- and p38MAPK-positive neurons, but upregulated phosphorylation of ERK1/2-positive neurons in the frontal cortex, and reduced the expressions of cleaved caspase-3, Bax, but increased Bcl-2 expressions in female rats exposed to TBI. CONCLUSIONS: Androgen was responsible for the enhanced susceptibility to TBI under melatonin supplementation in females through a mechanism that may be associated with MAPK pathway regulation.

Casein Kinase 2 Interacting Protein-1 Suppresses Glioma Cell Proliferation via Regulating the AKT/GSK3ß/ß-Catenin Pathway.

OBJECTIVE: Casein kinase 2 interacting protein-1 (CKIP-1) has exhibited multiple functions in regulating cell proliferation, apoptosis, differentiation, and cytoskeleton. CKIP-1 also plays an important role as a critical regulator in tumorigenesis. The aim of this study is to further examine the function of CKIP-1 in glioma cells. METHODS: The expression level of CKIP-1 protein was determined in gliomas tissues and cell lines by immunohistochemistry stain and western blotting while the association of CKIP-1 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. CKIP-1 was overexpressed or silenced in gliomas cell lines. CCK-8, colony formation assay, and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis. Cell cycle and apoptosis rate were determined with fluorescence-activated cell sorting (FACS) method. Then, expression of key members in AKT/GSK3ß/ß-catenin pathway was detected by western blot analysis. RESULTS: In the present study, we reported new evidence that CKIP-1 was reversely associated with the proliferation of glioma cells and survival in glioma patients. Additionally, the overexpressed CKIP-1 significantly inhibited glioma cell proliferation. Further experiments revealed that CKIP-1 functioned through its antiproliferative and proapoptotic activity in glioma cells. Importantly, mechanistic investigations suggested that CKIP-1 sharply suppressed the activity of AKT by inhibiting the phosphorylation, markedly downregulated the phosphorylated GSK3ß at Ser9, and promoted ß-catenin degradation. CONCLUSIONS: Overall, our results provided new insights into the clinical significance and molecular mechanism of CKIP-1 in glioma, which indicated CKIP1 might function as a therapeutic target for clinical treatment of glioma.

Antibiotic prophylaxis for infections in patients with acute stroke: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Infections are frequent after stroke and lead to increased mortality and neurological disability. Antibiotic prophylaxis has potential of decreasing the risk of infections and mortality and improving poor functional outcome. Several studies evaluated antibiotic prophylaxis for infections in acute stroke patients have generated conflicting results. The systematic review of randomized clinical trials (RCTs) aimed at comprehensively assessing the evidence of antibiotic prophylaxis for the treatment of acute stroke patients. MATERIALS AND METHODS: PubMed, EMBASE, the Cochrane library and the reference lists of eligible articles were searched to identify all potential studies. We included the studies that investigated the efficacy and safety of antibiotic prophylaxis for the treatment of acute stroke patients. The primary outcome included mortality and infection rate. The secondary outcomes included poor functional outcome and adverse events. RESULTS: Seven trials randomizing 4,261 patients were included. Pooled analyses showed that antibiotic prophylaxis did not improve the mortality (risk ratio (RR) = 1.03, 95% confidence interval (CI) 0.84 to 1.26, p = 0.78, I2 = 25%) and poor functional outcome (RR = 0.93, 95% CI 0.80 to 1.08, p = 0.32, I2 = 80%), but reduced the incidence of infection (RR = 0.67, 95% CI 0.53 to 0.84, p = 0.0007, I2 = 49%). No major side effects were reported. Sensitivity analyses confirmed the results of infection rate and poor functional outcome. CONCLUSIONS: Antibiotic prophylaxis can be used to treat the infectious events of acute stroke patients although it has no potential of decreased mortality and improved functional outcome.