Oral administration of honokiol attenuates airway inflammation in asthmatic mouse model.

Allergic asthma is a disease that pathologically characterized by eosinophilia infiltration, airway inflammation and hyper responsiveness. In this study, we evaluated the anti-inflammatory and anti-allergy possibilities of honokiol, a bi-phenolic compound obtained from species of the genus Magnolia, which has long been involved in traditional Chinese prescriptions for asthma-related lung diseases, in an ovalbumin-induced mouse model of allergic asthma. We found honokiol significantly inhibited the eosinophilia infiltration, reduced the airway inflammation and suppressed the production of inflammatory cytokines) as well as the IgE in serum. Moreover, MMP-9 and? (IL-4 and IFN- NF-κB were found to be involved in the honokiol induced biological process. These results suggested that honokiol may be a possible candidate in the treatment of lung asthma related diseases.

Association Between Isolated Single Umbilical Artery and Perinatal Outcomes: A Meta-Analysis.

BACKGROUND To evaluate the association between the isolated single umbilical artery (iSUA) and perinatal outcomes, including pregnancy outcomes and perinatal complications. MATERIAL AND METHODS We performed a meta-analysis of 15 eligible studies regarding the relationship between the iSUA and perinatal outcomes, including gestational age at delivery, nuchal cord, placental weight, small for gestational age (SGA), oligohydramnios, polyhydramnios, pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), preeclampsia, and perinatal mortality. The overall odds ratios (OR) or standardized mean difference (SMD) were calculated. RESULTS The occurrence of nuchal cord was not found to be different between an iSUA and a three-vessel cord (TVC) fetus. For perinatal complications, the SGA, oligohydramnios, polyhydramnios, GDM, and perinatal mortality showed dramatic difference between women with an iSUA and women with a TVC fetus, which implied that the presence of iSUA significantly increased the risk of perinatal complications. For other perinatal complications, such as PIH and preeclampsia, no significant association was detected. CONCLUSIONS Our meta-analysis suggests that the presence of iSUA would increase the risk of perinatal complications such as SGA, oligohydramnios, polyhydramnios, GDM, and perinatal mortality. Therefore, pregnant women with an iSUA fetus have poorer perinatal outcomes and more attention should be given to the management of their pregnancy compared to women with a TVC fetus.

Relationship between unexplained recurrent pregnancy loss and 5,10-methylenetetrahydrofolate reductase) polymorphisms.

OBJECTIVE: To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of folate metabolism-related genes. DESIGN: A case-control study. SETTING: Urban university-based hospital. PATIENT(S): Two-hundred and eighteen women with URPL and 264 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fluorescence quantitative polymerase chain reaction examination of sequences of the C677T and A1298C loci of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. RESULT(S): The frequency of the T allele at the MTHFR C677T locus in the URPL group was statistically significantly higher compared with the control group (odds ratio [OR] 1.324; 95% confidence interval [CI], 1.014-1.729), and the presence of the CC+CT genotype was statistically significantly reduced in the URPL group (OR 0.678; 95% CI, 0.471-0.974). The frequency of the C allele at the MTHFR A1298C locus in the URPL group was statistically significantly higher than that in the control group (OR 1.557; 95% CI, 1.066-2.275), and the presence of the CC+AC genotype was statistically significantly elevated in the URPL group (OR 1.740; 95% CI, 1.137-2.661). The frequency of MTHFR 677CT/1298AC compound genotypes in the URPL group was 6.589-fold higher compared with the control group. Most patients in the URPL group carried two mutant genes (69.3%), and the percentage of patients with two mutant genes was statistically significantly higher than in the control group (OR 4.996; 95% CI, 1.650-15.129). CONCLUSION(S): The MTHFR 1298AC genotype and composite heterozygote genotype (677CT/1298AC) are risk factors for URPL. The risk of URPL is highest in women carrying two mutations of A1298C and C677T locus in MTHFR.

The Risk Factors and Neonatal outcomes of Isolated Single Umbilical Artery in Singleton Pregnancy: A Meta-analysis.

The current meta-analysis aims to evaluate the risk factors and neonatal outcomes of isolated Single Umbilical Artery (iSUA) in singleton pregnancy. Standard Mean Difference (SMD) or Weighted Mean Difference (WMD) was pooled for the maternal age, gravidity and parity, neonate birth weight and Apgar score one and five minutes after birth. We also pooled the odds ratios (ORs) at 95% confidence intervals (CIs) for maternal smoking status, the rate of neonate delivery before 37 or 34 weeks, Cesarean section (CS), the rate of being admitted to neonatal intensive care unit (NICU) and the serious adverse neonate outcome. Results show that maternal primigravidity [OR: -0.082, CI (-0.152, -0.011), p = 0.023] and female sex of the neonate [OR: 0.805, CI (0.673, 0.963), p = 0.017] were associated with higher risks of iSUA. As compared to normal neonates, the neonates with iSUA had lower birth weight, worse Apgar score, increased risk of delivery before the normal gestational age, increased rate of CS due to fetal distress, increased rate of admission to NICU and prolonged NICU stay. However, no difference in neonatal mortality was observed. Maternal primigravidity and female neonate might associate with increased risk of iSUA. Identification of iSUA is of great importance for prenatal diagnosis and may improve neonatal outcomes.

Expression of CRM1 and CDK5 shows high prognostic accuracy for gastric cancer.

AIM: To evaluate the predictive value of the expression of chromosomal maintenance (CRM)1 and cyclin-dependent kinase (CDK)5 in gastric cancer (GC) patients after gastrectomy. METHODS: A total of 240 GC patients who received standard gastrectomy were enrolled in the study. The expression level of CRM1 and CDK5 was detected by immunohistochemistry. The correlations between CRM1 and CDK5 expression and clinicopathological factors were explored. Univariate and multivariate survival analyses were used to identify prognostic factors for GC. Receiver operating characteristic analysis was used to compare the accuracy of the prediction of clinical outcome by the parameters. RESULTS: The expression of CRM1 was significantly related to size of primary tumor (P = 0.005), Borrmann type (P = 0.006), degree of differentiation (P = 0.004), depth of invasion (P = 0.008), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and distant metastasis (P = 0.015). The expression of CDK5 was significantly related to sex (P = 0.048) and Lauren's classification (P = 0.011). Multivariate Cox regression analysis identified that CRM1 and CDK5 co-expression status was an independent prognostic factor for overall survival (OS) of patients with GC. Integration of CRM1 and CDK5 expression could provide additional prognostic value for OS compared with CRM1 or CDK5 expression alone (P = 0.001). CONCLUSION: CRM1 and CDK5 co-expression was an independent prognostic factors for GC. Combined CRM1 and CDK5 expression could provide a prognostic model for OS of GC.

Interleukin-8 serum levels in patients with hepatocellular carcinoma: correlations with clinicopathological features and prognosis.

PURPOSE: In this study, we measured the serum interleukin-8 (IL-8) levels in patients with hepatocellular carcinoma (HCC) to evaluate its correlation with clinicopathological features and prognosis. EXPERIMENTAL DESIGN: ELISA was used to detect the concentrations of IL-8, vascular endothelial growth factor, and macrophage migration inhibitory factor in preoperative sera of 59 patients with resection of HCC and 15 healthy subjects. RESULTS: Preoperative serum IL-8 was found to be significantly elevated in patients with HCC compared with healthy subjects (median, 17.6 versus 1.0 pg/ml, P=0.046). The levels of IL-8 correlated significantly with a large tumor size (>5 cm), absence of tumor capsule, presence of venous invasion, and advanced pathological tumor-node-metastasis stage. Serum IL-8 level was a significant prognostic factor in terms of disease-free and overall survival. Patients with a serum IL-8 level of >17.6 pg/ml had a poorer disease-free survival than those with a level of <17.6 pg/ml (median disease-free survival 4.7 versus 19.2 months). Multivariate analyses showed that serum IL-8 level was a significant and independent prognostic factor of survival. CONCLUSIONS: Significant correlations of serum IL-8 levels with tumor size and tumor stage suggest that IL-8 may be directly or indirectly involved in the progression of HCC. These findings indicate that serum IL-8 may be a useful biological marker of tumor invasiveness and an independent prognostic factor for patients with HCC.

Insulin in University of Wisconsin solution exacerbates the ischemic injury and decreases the graft survival rate in rat liver transplantation.

BACKGROUND: Insulin keeps the liver in a metabolically vigorous state. However, organ preservation aims to decrease the metabolic rate. The objective of this study was to clarify the effect of insulin used in University of Wisconsin (UW) preservation solution on the liver graft. METHODS: The liver grafts were preserved by UW solution with or without insulin for 7, 9, and 24 hr, respectively. The influence of insulin was studied by 7-day survival rate, liver function, morphology, and intragraft gene expression 24 hr after transplantation. Morphology was studied on the preserved grafts. RESULTS: The morphology of the graft in the insulin group showed more severe ischemia-reperfusion injury. The 7-day graft survival rates of the 7-hr subgroups with and without insulin were 55% and 93%, respectively (P=0.02). In the 9-hr subgroups, the survival rates were 0% and 78%, respectively (P=0.002). The serum levels of aspartate aminotransferase (AST) (P=0.008) and alanine aminotransferase (ALT) (P=0.032) were higher in the 7-hr subgroup with insulin. The same trend was found in the 9-hr subgroups (AST, P=0.016; ALT, P=0.016). The expression level of 215 genes were much lower at 24 hr after transplantation in the grafts preserved with insulin than in those preserved without insulin, and most of the genes were related to metabolic activities. CONCLUSIONS: Insulin in UW solution may exacerbate graft ischemic injury and decrease the graft survival rate in rat liver transplantation. Insulin, in the absence of glucose in UW solution, may exhaust the metabolic activity of the liver graft. It is harmful rather than helpful for isolated rat liver grafts preserved in UW solution.

Distinct intragraft response pattern in relation to graft size in liver transplantation.

BACKGROUND: The molecular mechanism of small-for-size graft injury remains unclear. The aim of this study is to investigate the gene expression pattern of acute phase response in relation to graft size in a rat-liver transplantation model. METHODS: A rat orthotopic liver transplantation model using 30%, 50%, and whole grafts was used. The graft survival rates and liver morphology were compared among the three groups. Two transcription factors, nuclear factor (NF)-kappaB (p65) and early growth response (Egr-1), and their downstream genes were compared. RESULTS: According to the graft size, the rats were grouped as follows: group 1 (n=20), 32% (24-47%); group 2 (n=10), 56% (50-65%); and group 3 (n=10), 104% (89-120%). The 7-day survival rates were 20% (P=0.039 vs. group 2, P=0.000 vs. group 3), 60%, and 100% in groups 1, 2, and 3, respectively. Dilation of hepatic sinusoids and vacuolization of hepatocytes were observed in group 1. Up-regulation of Egr-1 and endothelin (ET)-1 and over-expression of nitric oxide synthase (iNOS) was found in group 1, but heme oxygenase (HO)-1 and A20 were down-regulated. At 24 hours after reperfusion, the intragraft protein level of heat-shock protein (Hsp)-70 was significantly lower in group 1 than that in group 3 (12.4 vs. 17.0 ng/mL, P=0.04). More apoptotic nuclei were found in group 1. CONCLUSIONS: Small-for-size graft injury was related to early over-expression of Egr-1 associated with up-regulation of ET-1 and deterioration of intracellular homeostasis reflected by down-regulation of Hsps and A20.

Influenza seasonality and predominant subtypes of influenza virus in Guangdong, China, 2004-2012.

BACKGROUND: Influenza surveillance is carried out in Guangdong province, southern China. A better understanding of influenza seasonality and predominant Subtypes of influenza virus in Guangdong can help to improve evidence-based prevention and control strategies for influenza in the future. MATERIALS AND METHODS: THERE ARE THREE CATEGORIES OF INFLUENZA SURVEILLANCE IN GUANGDONG: Influenza-like Illness (ILI) Outpatient Surveillance, ILI Outbreak Surveillance and Influenza Virus Surveillance. This paper summarizes collected influenza surveillance data from January 2004 to December 2012 in Guangdong province. Time series analysis and "peak analysis" were performed to estimate seasonality and temporal trends of influenza activity. RESULTS: During the 9-year study period, a total of 37,571,582 outpatients had been recorded, in which 1,889,684 ILI cases had been reported. The provincial ILI visiting percentage peaked at 6-10%. A total of 107,115 respiratory specimens of ILI outpatients were collected, 17,454 (16.29%) of them tested for influenza virus were positive. Influenza virus peaks appeared in summer mostly with a median epidemic duration of 6 months. A total of 925 outbreaks recorded and 45,322 cases in which were affected. The majority of reported outbreaks (832 outbreaks, 90%) occurred in institutional settings. CONCLUSIONS: Influenza circulates periodically every year in Guangdong. Influenza activity had strong and clear seasonality with epidemic periods in summer for last decade. The presence of local unique seasonal pattern and its changes emphasizes the need to optimize timing of influenza vaccine delivery and other public health interventions.

Temporal trends of influenza A (H1N1) virus seroprevalence following 2009 pandemic wave in Guangdong, China: three cross-sectional serology surveys.

BACKGROUND: To evaluate the temporal trends of seroprevalence to pH1N1 among the Guangdong population following 2009 H1N1 pandemic wave, we conducted three cross-sectional serology surveys in 2010. METHODOLOGY/PRINCIPAL FINDINGS: Three surveys were carried out consecutively in 2010 from January 8 to January 24, from March 15 to April 10 and from August 23 to September 4. Sample populations comprising of 4725, 4727, and 4721 subjects respectively were randomly selected for study in these three surveys. The level of antibodies against pH1N1 was evaluated by hemagglutination inhibition assay. In survey 1, the seroprevalence of pH1N1 among all the subjects is 25.1%, declining to 18.4% in survey 2 and increasing to 21.4% in survey 3. Among vaccinated subjects, the seroprevalence was 49.0%, 53.0%, and 49.4% in the three consecutive surveys, showing no significant differences. In contrast, among non-vaccinated subjects, the seroprevalence declined significantly from 22.8% (survey 1) to 14.3% (survey 2) and subsequently increased to 18.1% (survey 3). The multivariate logistic regression analysis revealed that seroprevalence to pH1N1 in non-vaccinated individuals correlated with the investigated order of the surveys, age, and region (all P<0.05). However, it was not correlated with gender (P = 0.650), seasonal influenza vaccination history (P = 0.402) and symptoms (P = 0.074). CONCLUSIONS/SIGNIFICANCE: In Guangdong, the seroprevalance to pH1N1 decreased initially and then rebounded modestly during the first 9 months following the 2009 pandemic wave. Our results suggest that the prevalence of pH1N1 is still correlated with age and population density during the post-pandemic period. An early end to the free pH1N1 vaccination program might be another important reason for the slight rebound in seroprevalance. Our study findings can help the Guangdong authorities to make evidence-based decisions about a long-term vaccination strategy and boost immunity in specific population groups (such as children and people living in the capital-city) to prevent further transmission in the future.

Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma.

Macrophage migration inhibitory factor (MIF) may contribute to multiple aspects of tumor progression, including control of cell proliferation, differentiation, cell survival and angiogenesis. However, the potential roles of MIF in regulating hepatocellular carcinoma (HCC) tumor cell migration and the expression of angiogenic factors by HCC tumor cells have not been studied yet. In our study, we reported that intracellular MIF mRNA and protein were overexpressed in HCC tissues compared to nontumor tissues by using in situ hybridization and immunohistochemic staining. HCC tumor cell lines also secreted large amounts of MIF into the supernatants of tumor cell culture. To assess the role of MIF in HCC, we employed the transwell invasion chamber to study the effect of MIF on tumor cell migration. Our results showed that recombinant MIF and the supernatants of tumor cell line culture could enhance the invasion and migration of HCC cells. This effect can be inhibited by the addition of a neutralizing anti-MIF antibody. We observed that increased MIF serum levels correlated with higher levels of interleukin-8 (IL-8) in the sera of patients with HCC than in normal volunteers. We therefore hypothesized that MIF may regulate the production of angiogenic factors by HCC cells. To test this hypothesis, we examined the effect of MIF treatment on vascular endothelial growth factor (VEGF) and IL-8 expression by HCC cell lines. MIF induced a significant dose-dependent increase in IL-8 and VEGF production. Taken together, our results indicated that MIF may act as an autocrine-acting factor that stimulates angiogenesis and metastasis in HCC by promoting expression of angiogenic factors and migration of tumor cells. A more detailed understanding of the MIF regulatory mechanisms involved may provide insight into new direction in the treatment of HCC.