Effects of in IL-1B/IL-1RN variants on the susceptibility to head and neck cancer in a chinese Han population.

BACKGROUND: The study aimed to evaluate the relationship of IL-1B/IL-1RN polymorphisms to the predisposition of head and neck cancer (HNC) in a Chinese Han population. METHODS: Nine single-nucleotide polymorphisms (SNPs) in IL-1B/IL-1RN were genotyped based on Agena MassARRAY platform. Logistic regression models were used to analyze the genetic association between these SNPs and HNC risk by calculating odds ratios (ORs) and 95% confidence intervals (CI). Haplotype analysis were performed using Haploview program and logistic regression model. RESULTS: The genetic association between rs1143643 in IL-1B and the higher risk of HNC was found (OR = 1.23, 95% CI 1.04-1.46) in the overall. IL-1RN rs17042888 was related to a reduced risk of HNC in the subjects aged > 46 years (OR = 0.70, 95% CI: 0.50-0.98) and in females (OR = 0.71, 95% CI 0.52-0.98), while rs1143643 increased the predisposition of HNC among females (OR = 1.76, 95% CI 1.13-2.74). Furthermore, rs1143643 had an increased susceptibility to thyroid carcinoma (OR = 1.61, 95% CI 1.10-2.34). Moreover, compared with stage I-II, the frequency of IL-1RN rs452204-AG genotype was lower in patients with stage III-IV. CONCLUSIONS: IL-1B (rs1143643) and IL-1RN (rs17042888 and rs452204) polymorphisms might be related to the individual susceptibility of HNC in the Chinese Han population. These results might help to improve the understanding of IL-1B and IL-1RN genes in the occurrence of HNC.

Quantitative Determination of Four Azo Dyes in Rat Plasma with Solid-Phase Extraction and UFLC-MS-MS Analysis: Application to a Pharmacokinetic Study.

A rapid and sensitive ultra-fast liquid chromatography tandem mass spectrometry method, followed by simple protein precipitation and solid-phase extraction, has been developed and validated for the quantitative determination of four azo dyes (Para red, Solvent yellow 2, Solvent red 1 and Sudan red 7B) in rat plasma using D5-Sudan I as the internal standard. The optimal separation was accomplished on an Agilent Eclipse Plus C18 column (100 × 2.1 mm, 1.8 µm) with gradient elution using the mobile phase including acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.45 mL/min. The detection was conducted by means of electrospray ionization mass spectrometry in positive ion mode with multiple reaction monitoring. The calibration curves showed good linearity, with correlation coefficients >0.998 for all of the analytes within the concentration range. The lower limits of quantification (LLOQs) of Para red, Solvent yellow 2, Solvent red 1 and Sudan red 7B in rat plasma were 1.0, 0.1, 0.1 and 0.1 µg/L, respectively. The intra- and interday relative standard deviations were ≤9.6 and ≤12.4%, respectively, and the accuracy was in the range of -5.8 to -9.5%. The average recoveries were between 81.49 and 118.65%, and the matrix effects were satisfactory in the biological matrices. The fully validated method has been successfully applied in measuring levels of the four azo dyes in rat plasma following oral administration of 20.0 mg/kg of analytes in rats, which was suitable for the pharmacokinetic studies of the azo dyes.

Upregulation of miR-137 protects anesthesia-induced hippocampal neurodegeneration.

PURPOSE: Ketamine is commonly used in pediatric anesthesia but may cause neurodegeneration in young brains. The aim of the study is to use an animal model to characterize the role of microRNA 137 (miR-137) in ketamine-induced neurodegeneration in neonatal hippocampus. METHODS: Young Sprague-Dawley Rats (1 month old) was systemically administrated with ketamine (75 mg/kg) for 3 days. TUNEL assay was used to assess the ketamine-induced neurodegeneration of hippocampal CA1 neurons, quantitative real-time PCR (qRT-PCR) to assess the expression of miR-137 and Morris water maze test (MWM) to assess the damaged memory function. Alternatively, lentivirus over-expressing miR-137 was injected into hippocampus before ketamine administration, and the subsequent effects of miR-137 upregulation on ketamine-induced hippocampal neurodegeneration and memory dysfunction were investigated. Furthermore, the direct downstream target of miR-137, CDC42, was down-regulated by siRNA injection into hippocampus. The effects of CDC42 inhibition on hippocampal apoptosis and memory function were also investigated. RESULTS: Excessive ketamine treatment resulted in severe apoptosis in hippocampal CA1 neurons, downregulation of miR-137 in hippocampus and significant long-term memory dysfunction. Conversely, pre-treatment of overexpressing miR-137 protected hippocampal neurodegeneration and memory loss. The molecular target of miR-137, CDC42 was down-regulated by ketamine in hippocampus. Knocking down hippocampal CDC42 exerted an apoptotic effect on hippocampal neurons and memory loss, similar to the effect of ketamine treatment. CONCLUSIONS: Our results demonstrated that miR-137 played an important role in regulating ketamine induced hippocampal neurodegeneration, possibly through CDC42.

Penehyclidine hydrochloride inhibits the LPS-induced inflammatory response in microglia.

BACKGROUND: Activated microglia play an important role in neuroinflammation, which contributes to the neuronal damage found in many neurodegenerative diseases. Penehyclidine hydrochloride (PHC) is an anesthetic used before surgical operations, but also exhibits anti-inflammatory effects on the respiratory and digestive system. In the present study, we investigated whether PHC produces similar anti-inflammatory effects in activated microglia in the central nervous system. MATERIALS AND METHODS: Microglial cells were incubated with lipopolysaccharide (LPS) in the presence or absence of various concentrations of PHC, SB203580 (p38 mitogen-activated protein kinase [MAPK] inhibitor), and pyrrolidine dithiocarbamate (nuclear factor-kappa B [NF-κB] inhibitor). Markers of inflammation and oxidative stress were measured using enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. The effect of PHC on NF-κB activity was assessed with a NF-κB p50/p65 transcription factor assay kit. The involvement of p38 MAPK phosphorylation in the anti-inflammatory effects of PHC was evaluated with a specific enzyme-linked immunosorbent assay kit for phospho-p38. RESULTS: PHC significantly inhibited the release of nitric oxide, prostaglandin E2, interleukin 1ß, and tumor necrosis factor α while upregulating the expression of inducible nitric oxide synthase messenger RNA in LPS-activated microglia. Moreover, PHC effectively inhibited the translocation of NF-κB from the cytoplasm to the nucleus and the phosphorylation of p38 MAPK. The activities of NF-κB and p38 MAPK in LPS-treated microglia were significantly lowered after pretreatment of PHC. CONCLUSIONS: PHC inhibited the LPS-induced release of inflammatory mediators in microglia. These inhibitory effects of PHC may be mediated by blocking p38 MAPK and NF-κB pathways in microglia. These preclinical findings may offer a novel therapeutic option to confine microglial overactivation in neurodegenerative diseases.

[Effect of curcumine on the nuclear pathway of JNK during hippocampal ischemia/reperfusion injury in SHR].

OBJECTIVE: To investigate the diversify of the nuclear pathway of c-Jun NH2-terminal kinases (JNK) during transient brain ischemia/reperfusion injury in hippocampal neuron apoptosis in spontaneously hypertensive rats (SHR) and to test whether the neuroprotection of curcumine on transient brain ischemia/reperfusion injury in SHR is related to the nuclear pathway of JNK. METHODS: Male Wistar-Kyoto (WKY) rats and SHR were randomly divided into five groups (n = 6): WKY sham group (W-Sham), WKY ischemia/reperfusion group (W-I/ R), SHR sham group (S-Sham), SHR ischemia/reperfusion group (S-I/R) and SHR curcumine (a chinese traditional medicine)100 mg/kg treatment group (S-Cur), which were sacrificed at 2 h, 6 h, 24 h, 3 d and 7 d after reperfusion. Global brain ischemic model was established by 4-VO method. The TdT-mediated dUTP nick end labeling (TUNEL) method was used to detect the neuron apoptosis in hippocampal CA1 region. The immunohistochemical method was applied to investigate the expressions of c-jun and c-fos in hippocampal CA1 region. RESULTS: The expressions of apoptosis and c-jun and c-fos in CA1 region in S-Sham group, W-I/R group and S-I/R group were more than those in W-Sham group (P < 0.05), were significantly increased in S-I/R group than those in W-I/R group (P < 0.05), and were significantly decreased in S-Cur group than those in S-I/R group (P < 0.05). CONCLUSION: Neuronal apoptosis and the expressions of c-jun and c-fos are more in SHR hippocampal. Global brain ischemia/reperfusion injury induces more expressions of apoptosis in hippocampal neuron in SHR, and the more expressions of c-jun and c-fos may participate in that process. The neuroprotection of curcumine in SHR is related to c-jun and c-fos.