Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation

Introduction. The exchange protein directly activated by cAMP (Epac1), a downstream target of the second messenger cAMP, modulates multiple biological effects of cAMP, alone or in cooperation with protein kinase A (PKC). Epac1 is necessary for promoting protein kinase C (PKC) translocation and activation. The aim of the study was to assess the intensity of Epac1 and protein kinase C (PKC) immunoreactivity in lung cancer and para-carcinoma tissues, and their associations with clinical-pathological indexes. Correlations between the immunoreactivity of Epac1, PKC, A-kinase anchor protein 95 (AKAP95) and connexin43 (Cx43) were also examined. Material and methods. Epac1, Cx43 (46 cases) and PKC, AKAP95 (45 cases) immunoexpression levels were determined in tissue samples of lung cancer and in 12 samples of neighboring para-carcinoma specimens by the PV-9000 Two-step immunohistochemical technique. Results. The percentage of Epac1 positive samples was significantly lower in lung cancer tissue than in neighboring para-carcinoma specimens (37% vs. 83.3%, p < 0.05); the difference in PKC immunoreactivity was not significant (64.4% vs. 91.7%). Epac1 expression was associated with the degree of malignancy and lymph node metastasis (P < 0.05), but not with histological type (P > 0.05), whereas PKC expression was not related to these parameters. Interestingly, Epac1 expression was correlated with PKC and Cx43 expression. Moreover, PKC expression was correlated with AKAP95 expression. Conclusion. Normal Epac1 expression may suppress lung cancer occurrence and metastasis, and its downregulation is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation.

Aire-Overexpressing Dendritic Cells Induce Peripheral CD4+ T Cell Tolerance

Autoimmune regulator (Aire) can promote the ectopic expression of peripheral tissue-restricted antigens (TRAs) in thymic medullary epithelial cells (mTECs), which leads to the deletion of autoreactive T cells and consequently prevents autoimmune diseases. However, the functions of Aire in the periphery, such as in dendritic cells (DCs), remain unclear. This study’s aim was to investigate the effect of Aire-overexpressing DCs (Aire cells) on the functions of CD4+ T cells and the treatment of type 1 diabetes (T1D). We demonstrated that Aire cells upregulated the mRNA levels of the tolerance-related molecules CD73, Lag3, and FR4 and the apoptosis of CD4+ T cells in STZ-T1D mouse-derived splenocytes. Furthermore, following insulin stimulation, Aire cells decreased the number of CD4+ IFN-γ+ T cells in both STZ-T1D and WT mouse-derived splenocytes and reduced the expression levels of TCR signaling molecules (Ca2+ and p-ERK) in CD4+ T cells. We observed that Aire cells-induced CD4+ T cells could delay the development of T1D. In summary, Aire-expressing DCs inhibited TCR signaling pathways and decreased the quantity of CD4+IFN-γ+ autoreactive T cells. These data suggest a mechanism for Aire in the maintenance of peripheral immune tolerance and provide a potential method to control autoimmunity by targeting Aire

Densities and Viscosities for Binary Mixtures of the Ionic Liquid <i>N</i>-Ethyl Piperazinium Propionate with <i>n</i>-Alcohols at Several Temperatures

A novel ionic liquid <i>N</i>-ethyl piperazinium propionate, [NEPP], was prepared, and the densities and viscosities for the binary mixtures of [NEPP] with methanol, ethanol, <i>n</i>-propanol, and <i>n</i>-butanol were measured over the whole concentration range at (298.15, 303.15, 308.15, and 313.15) K and 0.1 MPa. The data of the excess molar volume, <i>V</i>_m^E, were calculated and fitted with the Redlich–Kister type polynomial equation. The values of <i>V</i>_m^E of the investigated systems are all negative, indicating that the ion–dipole interactions play important roles between the molecules of the ionic liquid and the alcohols

Extraction of Aromatics from Hydrocarbon Fuels Using <i>N</i>-Alkyl Piperazinium-Based Ionic Liquids

A total of 10 new <i>N</i>-alkyl piperazinium-based ionic liquids (ILs) have been prepared, and they are used as extractants for removing aromatics from three kinds of hydrocarbon fuels. A total of 3 ILs, <i>N</i>-methyl piperazinium lactate (MPL), <i>N</i>-ethyl piperazinium lactate (EPL), and <i>N</i>-ethyl piperazinium propionate (EPP), in the liquid state at room temperature are used directly for extraction, while the other 7 ILs in the solid state at room temperature are used with methanol as the co-solvent. Effects on the extraction efficiency of the temperature and the amounts of IL and co-solvent are investigated. The results indicate that the amounts of IL and co-solvent play very important roles in the extraction process and the efficiency is greatly influenced by the cation and anion structures in the <i>N</i>-alkyl piperazinium-based ILs. In comparison to 1,1,3,3-tetramethylguanidinium lactate (TMGL), the extraction capability order is EPP > EPL > MPL > TMGL. The ILs with aromatic anions are found to have better extraction capability than the others. Furthermore, recycling of ILs reflects that these ILs can be recovered simply by vacuum distillation without a significant decrease in the activity of dearomatization

Aerobic Degradation Characteristics of Decabromodiphenyl ether through Rhodococcus ruber TAW-CT127 and Its Preliminary Genome Analysis

Decabromodiphenyl ether (BDE-209), a polybrominated diphenyl ether (PBDE) homolog, seriously threatens human health. In this study, a Rhodococcus ruber strain with high BDE-209 degradation activity, named TAW-CT127, was isolated from Tong&rsquo;an Bay, Xiamen. Under laboratory conditions, the strain&rsquo;s optimal growth temperature, pH, and salinity are 45 &deg;C, 7.0, and 0&ndash;2.5%, respectively. Scanning electron microscopy (SEM) analysis shows that TAW-CT127 is damaged when grown in manual marine culture (MMC) medium with BDE-209 as the sole carbon source instead of eutrophic conditions. In the dark, under the conditions of 28 &deg;C, 160 rpm, and 3 g/L (wet weight) TAW-CT127, the degradation rate of 50 mg/L BDE-209 is 81.07%. The intermediate metabolites are hexabromo-, octabromo-, and nonabromo-diphenyl ethers. Through whole-genome sequencing, multiple dehalogenases were found in the genome of TAW-CT127; these may be involved in the production of lower-brominated diphenyl ethers. Additionally, biphenyl-2,3-dioxygenase (BDO) in TAW-CT127 may catalyze the debromination reaction of BDE-209. Our research provides a new high-efficiency strain for bioremediation of BDE-209 pollution, and lays the foundation for the preliminary exploration of genes associated with BDE-209 degradation

Efficacy of a Recombinant Genotype VII Vaccine against Challenge with Velogenic Newcastle Disease Virus

Background: Newcastle disease virus (NDV) genotype VII has become the dominant genotype in China. However, NDV genotype II was used to make current commercial NDV vaccines. The mismatch of genotypes between circulating and vaccine strains of viruses may compromise the efficacy of vaccines. Methods: In this study, a current circulating NDV was attenuated by mutations of multiple basic amino acid motif of fusion cleavage site 112RRQKGF117 based on reverse genetic techniques. The recombinant virus was prepared as an inactivated vaccine to test its efficacy and compared with a commercial LaSota NDV vaccine on SPF chickens.Results: All vaccinated chickens survived by the end of the study. By contrast, the unvaccinated chickens were all dead before 5 days post-challenge (DPC). Compared to commercial LaSota vaccine, the experimental inactivated vaccine elicited earlier and higher titer of HI antibodies and had reduced titer and duration of virus shedding after challenge. Conclusion: The experimental inactivated NDV vaccine may work as a promising vaccinecandidate to control the disease.</p