[Effect of curcumin on intestinal mucosal mechanical barrier in rats with non-alcoholic fatty liver disease].

Objective: To investigate the effect of curcumin on intestinal mucosal mechanical barrier in rats with non-alcoholic fatty liver disease. Methods: A total of 30 male Sprague-Dawley rats were equally divided into normal control group, model group, and curcumin intervention group. The rats in the model group and the curcumin intervention group were given high-fat feed for 16 weeks, and those in the curcumin intervention group were given curcumin 200 mg/kg/day by gavage once a day after 8 weeks of high-fat feeding. The rats were sacrificed at the end of week 16. A light microscope was used to observe pathological changes in the liver, an electron microscope was used to observe the tight junction of the intestinal mucosa, an automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), chromogenic substrate Limulus amebocyte lysate assay was used to measure plasma lipopolysaccharide (LPS) level, spectrophotometric method was used to measure the activity of serum diamine oxidase, ELISA was used to measure the serum level of tumor necrosis factor-α (TNFα), and immunohistochemistry was used to measure the expression of the tight junction protein occludin. One-way ANOVA test and SNK-q test were used for statistical analysis. Results: Under the light microscope, the control group had no hepatocyte steatosis, the model group had significant hepatocyte steatosis and inflammatory cell infiltration, and the curcumin intervention group had reduced hepatocyte steatosis and inflammatory cell infiltration. Under the electron microscope, the control group had a clear and complete structure of the tight junction of the intestinal mucosa and normal structures of mitochondria and endoplasmic reticulum; in the model group, the structure of the tight junction of the intestinal mucosa was destroyed, the intercellular space was widened, the desmosomes had a loose structure, there was edema in some mitochondria, and the endoplasmic reticulum was dilated; the curcumin intervention group had improvements in the structure of tight junction of the intestinal mucosa, intercellular space, edema in the mitochondria, and dilation of the endoplasmic reticulum. Compared with the control group, the model group had significant increases in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = -15.918, -14.402, -33.700, -8.944, and -10.832, P < 0.05); compared with the model group, the curcumin intervention group had significant reductions in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = 10.457, 7.752, 18.802, 5.202, and 4.279, P < 0.05). In the control group, occludin showed a linear distribution along the top of small intestinal mucosal epithelial cells. The model group had a significant reduction in positive staining compared with the control group, and the curcumin intervention group had a significant increase in positive staining compared with the model group. The relative expression of occludin was 0.29±0.03 in the control group, 0.12±0.02 in the model group, and 0.21±0.02 in the curcumin intervention group (P < 0.05). Conclusion: Intestinal mucosal mechanical barrier is impaired in rats with NAFLD. Curcumin can reduce such damage, and its mechanism of action may be related to up-regulating the expression of occludin in the intestinal mucosa and reducing the levels of TNFα and LPS.

Association of p53 Arg72Pro and MDM2 SNP309 polymorphisms with glioma.

Epidemiological studies of the association of variants p53 Arg72Pro and MDM2 single-nucleotide polymorphism 309 (SNP309) with glioma risk have produced inconsistent results. The aim of the current study was to evaluate the association of these 2 variants with glioma susceptibility using a meta-analysis approach. For p53 Arg72Pro, 10 case-control studies including 2587 glioma patients and 4061 unrelated controls were identified. The pooled odds ratios (ORs) for Arg/Pro heterozygotes and Pro/Pro homozygotes were 1.08 [95% confidence interval (95%CI) = 0.85-1.37] and 1.08 (95%CI = 0.85-1.36), respectively, when compared to Arg/Arg carriers. Under the dominant effect model, Pro allele carriers also showed no significantly elevated glioma risk (pooled OR = 1.11, 95%CI = 0.90-1.38), and similar results were found under the recessive-effect model (pooled OR = 1.17, 95%CI = 0.85-1.61). For variant MDM2 SNP309, 3 case-control studies including 606 cases and 309 controls were identified. A marginal association with glioma risk was found for heterozygous G/T carriers (pooled OR = 1.95, 95%CI = 1.00- 3.81), whereas homozygous G/G carriers showed an increased but not significantly elevated risk of glioma (pooled OR = 2.14, 95%CI = 0.71-6.45) compared with that of T/T homozygotes. We also found no significant association between the MDM2 SNP309 polymorphism and glioma risk (pooled OR = 1.86, 95%CI = 0.94-3.67 and pooled OR = 1.25, 95%CI = 0.62-2.56, respectively) under the dominant and recessive models. Taken together, the current data suggested that the 2 polymorphisms may not contribute to glioma susceptibility.

Tramadol requirements may need to be increased for the perioperative management of pain in smokers.

Evidence indicates that smokers have hyperalgesia perioperatively as characterized by a higher postoperative pain score as well as increased requirements of opioids during surgery and postoperative patient-controlled analgesia compared with non-smokers. The possible mechanism of hyperalgesia for smokers is related to nicotinic acetylcholine receptor (nAChR) desensitization as well as competitive occupancy for binding sites. For smokers, high doses of opioids are needed perioperatively whereas small doses of nicotine do not reduce postoperative opioid requirements. Nicotine replacement treatment has been proved to be effective only for non-smokers. The serotonergic system plays an important part in modulating anti-nociception, and decreasing the concentration of serotonin in vesicles in neurons of the brain and spinal cord is an effective method. Intraoperative application of tramadol could result in an analgesic effect via enhancement of descending inhibitory pain pathways. Therefore, increasing the amount of tramadol given intraoperatively and postoperatively may reduce overall opioid requirements, and decrease the pain score as well as morphine consumption postoperatively.

Down-regulation of 67LR reduces the migratory activity of human glioma cells in vitro.

OBJECTIVES: Glioma is the most common brain tumor in central nervous system. Traditional therapies are not effective to cure this disease. Experimental evidence indicates that the 67 kDa elastin-laminin receptor (67LR) subunit is a high-affinity non-integrin laminin-binding protein that is over-expressed on the tumor cell surface in a variety of human carcinomas, and directly correlates with a higher proliferation rate of malignant cells and tendency to metastasize. However, little is known of the expression and function of 67LR in glioma cells. METHODS: In this study, we estimated whether 67LR was constitutively over-expressed in high-grade astrocytomas by immunohistochemical staining and Western blotting, and investigated the role of a low level of 67LR expression in glioma cell line-U251 by constructing an interfering RNA expression plasmid. RESULTS: The results showed that the 67LR had an enhanced over-expression in high-grade astrocytomas against normal brain tissues samples, and that the migratory activity of glioma cells was reduced after the down-regulation of the 67LR gene by RNAi. DISCUSSION: It was hypothesized that a low level of 67LR expression could reduce migratory activity of glioma cells, which further proved that 67LR played an important role in glioma invasion by mediating tumor cell functions leading to sarcomata. This study provided a new alternative to gene therapy for glioma treatment.