The expression and significance of dishevelled in human glioma

Background

The proto-oncogene dishevelled (Dvl) is a critical component of the Wnt/β-catenin signaling pathway, and its elevated expression in various tumor types is associated with malignancy. However, a role for Dvl in glioma has not been explored.

Materials and methods

To determine whether Dvl expression is elevated in human glioma, we examined the protein levels in 67 human glioma samples and 3 normal brain specimens by Western blotting and immunohistochemistry. To investigate a possible association of Dvl with the malignant phenotype in glioma, the correlation of the Dvl immunoreactivity score (IRS) with β-catenin IRS, the tumor proliferation index (PI), and tumor invasion index (II) were determined for each sample.

Results

The Dvl IRS, β-catenin IRS, PI, and II increased significantly with the pathologic grade of glioma (P <0.001) with average scores of 3.46 ± 3.45, 3.92 ± 3.28, 30.93 ± 17.92, and 20.43 ± 11.79, respectively. Furthermore, the PI and II were significantly higher for the Dvl-positive group than the Dvl-negative group (P <0.001). Correlation analysis demonstrated that β-catenin IRS, PI, and II were positively correlated with Dvl IRS.

Conclusions

Dvl overexpression may contribute to the malignant proliferation and invasion of human glioma.     

Mash1 efficiently reprograms rat astrocytes into neurons简

To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mashl and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examined astrocytes from 2-month-old Sprague-Dawley rats, and found that Brn2 was expressed, but Mashl was not detectable. Thus, we hypothesized that Mashl alone could be used to reprogram astrocytes into neurons. We transfected a recombinant MSCV-MASH1 plasmid into astrocytes for 72 hours, and saw that all cells expressed Mashl. One week later, we observed the changes in morphology of astrocytes, which showed typical neuro- nal characteristics. Moreover, β-tubulin expression levels were significantly higher in astrocytes expressing Mashl than in control cells. These results indicate that Mashl alone can reprogram astrocytes into neurons.     

Genes in the serotonin pathway are associated with bipolar affective disorder in a Han Chinese population

Serotonin plays an important role in mood regulation, but the involvement of serotonin pathway genes in the development of bipolar I disorder (BP-I), a mood disorder, is not clear. We selected 21 singlenucleotide polymorphisms (SNPs) within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP-I and 475 normal controls were recruited. Two out of 21 SNPs (rs1475196 and rs9567747) in the HTR2A gene and 1/23 SNPs (rs17110566) in the TPH2 gene were significantly associated with BP-I, both genotype-wise and allele-wise. Furthermore, a specific haplotype in the HTR2A gene showed a significant association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the serotonin pathway play important roles in susceptibility to BP-I.     

GC-MS/MS法测定桂丁香中β-谷甾醇含量

目的：在《江苏省中药饮片炮制规范》修订时,增加MS测定中药材桂丁香中β-谷甾醇的含量。方法：采用气相色谱-串联质谱法（GC-MS/MS）,大气压电喷雾离子源,负离子模式,多反应检测（MRM）定性离子对（m/z）329.0/95.2和定量离子对329.0/189.2,精确测定了β-谷甾醇含量。结果：β-谷甾醇在4.97~49.7 ng范围内线性关系良好（r=0.999 5）,平均回收率为99.4%,RSD为1.4%（n=6）。结论：本方法操作简便,专属性强,检测灵敏度高,重复性好,可测定桂丁香中β-谷甾醇的含量。     

Subclinical infections of cardiac implantable electronic devices: Insights into the host–bacteria dialog from blood and pocket tissue with pyrosequencing

While bacteria exist in CIED patients without clinical signs of infection, the underlying bacterial community structure and diversity in the bloodstream and pocket tissue of asymptomatic CIED patients remain unknown. In this study, we performed high-throughput 454 pyrosequencing of bacterial 16S rDNA of blood and pocket tissue from 54 asymptomatic CIED patients as well as blood from 30 normal individuals (normal controls). Firstly, we observed a significant increase of blood bacterial diversity in patients as compared with blood of normal subjects or patient tissues. We also found significant differences in 13 blood-associated bacterial genera between patients and normal subjects, and 14 bacteria genera between blood and tissues within patients. Secondly, we found that the serum levels of four inflammatory markers (CRP, IL-1β, IL-6, and MCP-1) in CIED patients were significantly higher than those in normal subjects. Thirdly, we found that there were significant correlations between 43 bacterial species and these inflammatory markers. Taken together, our results reveal a high diversity in the microbial community in CIED patients, and suggest the potential roles of multiple bacteria co-occurrence in the CIED subclinical infections.     

Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation,and up-regulates ATP-binding cassette transporterA1 in atherosclerosis

Atherosclerosis (AS) is a chronic inflammatory disease of the arterial wall. Macrophages are considered to be closely associated with the development and progression of AS. However, the precise mechanism of miR-17-5p in the macrophages under AS remains incompletely clarified. This study investigated the regulatory effect of miR-17-5p on the inflammation and lipid accumulation in mouse macrophages both in vivo and in vitro. It was found that miR-17-5p was highly expressed with lowered ATP-binding cassette transporterA1 (ABCA1) level in the peripheral blood leucocytes (PBLs) of AS patients. Moreover, the level of miR-17-5p was up-regulated in the macrophages of ApoE^?/? mice fed with a high-cholesterol diet. Furthermore, we injected miR-17-5p antagomir into AS mice or transfected miR-17-5p inhibitors into mouse macrophage RAW264.7 cells. Results showed that downregulation of miR-17-5p significantly reduced the production of inflammatory cytokines, inhibited the lipid accumulation and up-regulated ABCA1, and activated peroxisome proliferator-activated receptor (PPAR) γ/Liver X receptor (LXR) α signaling pathway. Additionally, ABCA1 was found to be a target of miR-17-5p by directly binding to 3′-untranslated region (3′-UTR) of its mRNA. Our study indicates a novel regulatory mechanism for miR-17-5p by interacting with ABCA1, which could be a therapy-target for the treatment of AS.     

Depression in older patients with advanced colorectal cancer is closely connected with immunosuppressive acidic protein

Colorectal cancer (CRC) is one of the most common tumors. CRC patients are susceptible to suffering from depression. Whether the immune system of CRC patients with depression is impaired or stimulated is controversial. Possible reasons for this conflict are the involvement of confounding factors, such as the age of the patient, the stage of the CRC and the types of treatment in previous studies. To demonstrate clearly the relationship between depression and the immune system in the context of CRC, the present study included only older patients with advanced CRC who received only chemotherapy, and the study adopted immunosuppressive acidic protein (IAP) as an immune parameter for the first time. A total of 56 older patients with advanced CRC completed the Zung Self-Rating Depression Scale (SDS) and were divided into two groups according to SDS scores. The patients exhibiting depression were treated with fluoxetine until their symptoms remitted. The serum levels of IAP and the percentages of CD3-positive (CD3+), CD4+, CD8+ T lymphocytes and CD56+ natural killer (NK) cells and Neutrophil-lymphocyte ratio (NLR) were calculated at the time of enrollment and once the symptoms remitted. Correlation analyses revealed that the SDS score was positively associated with serum IAP levels but negatively associated with CD3 and CD4 levels. Among the depressed and non-depressed patients, serum IAP levels and the percentages of CD3 and CD4 cells were dramatically different. After the depression symptoms were treated, the IAP levels dramatically decreased, while the levels of CD3, CD4, CD8 and CD56 were unchanged. All of above suggested that IAP was closely correlated with depression and might be a relatively objective parameter for predicting depression.     

Characterization of the Partition Rate of Ibuprofen Across the Water-Octanol Interface and the Influence of Common Pharmaceutical Excipients

This work reports the measurement of the partition rate of a model drug, ibuprofen (IBU), from aqueous solutions into octanol in the absence and presence of common pharmaceutical excipients including glucose, lactose, maltoheptaose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyvinylpyrrolidone–vinyl acetate, hydroxypropyl methylcellulose AS, sodium dodecyl sulfate, Tween 80, and sodium taurocholate at varying concentrations. This attempts to assess the kinetic aspect of IBU partitioning across the water-octanol interface by applying a mechanistic model and to characterize the interfacial resistance. A significant reduction in P_i across the water-octanol interface was observed with extremely low concentration of the selected excipients in the aqueous media. These results reveal the presence of a surface excess of adsorbed excipients at the water-octanol interface. The retardation of the P_i of IBU was found to be sensitive to (1) the molecular weight or the degree of polymerization of these excipients, (2) the hydrodynamic condition of the experimental method, and (3) the pH of the aqueous media. Retardation of the P_i of IBU in the presence of excipients observed in this study is proposed by a steric obstruction mechanism through the adsorbed surface excess layer of excipients located at the water-octanol interface.