Actions of endomorphins on synaptic transmission of aδ-fibers in spinal cord dorsal horn neurons

The effects of endogenous mu-opioid ligands, endomorphins, on Adelta-afferent-evoked excitatory postsynaptic currents (EPSCs) were studied in substantia gelatinosa neurons in spinal cord slices. Under voltage-clamp conditions, endomorphins blocked the evoked EPSCs in a dose-dependent manner. To determine if the block resulted from changes in transmitter release from glutamatergic synaptic terminals, the opioid actions on miniature excitatory postsynaptic currents (mEPSCs) were examined. Endomorphins (1 microM) reduced the frequency but not the amplitude of mEPSCs, suggesting that endomorphins directly act on presynaptic terminals. The effects of endomorphins on the unitary (quantal) properties of the evoked EPSCs were also studied. Endomorphins reduced unitary content without significantly changing unitary amplitude. These results suggest that in addition to presynaptic actions on interneurons, endomorphins also inhibit evoked EPSCs by reducing transmitter release from Adelta-afferent terminals.     

Assessment of genetic differentiation in the large yellow croaker, Pseudosciaena crocea Richardson,and its first hybrid filial generations with AFLP markers

The genetic diversity (the digital characteristics) of four populations (120 individuals) of breeding large yellow croakers, Pseudosciaena crocea Richardson, was analyzed with amplified fragment length polymorphism (AFLP) markers. Ten primer combinations amplified 248 bands, of which 39.52% were polymorphic. Shannon's information index of the Daiqv (DQ) population was higher than that of the Minyu (MY) population, at 0.2167 and 0.2074, respectively. Additionally, the Shannon's information index value for the minus-hybrid (DQ population♂ × MY population♀) first hybrid generation was higher than the value for the plus-hybrid (MY population♂ × DQ population♀) first hybrid generation at 0.1687 and 0.1613, respectively. The F_ST of the parental generation was lower than that of the filial generation at 0.0329 and 0.0891, respectively. Gene flow was very high according to F_st values in both parental and filial generations. The UPGMA clustering analysis based on genetic similarity organized the four populations into three groups. The minus-hybrid stock was the most distinct as compared to the other populations.     

Expression of four <Emphasis Type="Italic">pha</Emphasis> genes involved in poly-β-hydroxybutyrate production and accumulation in <Emphasis Type="Italic">Rhodobacter sphaeroides</Emphasis> FJ1

A cluster of genes encoding polyhydroxybutyrate (PHB) depolymerase (phaZ), PHB synthase (phaC), phasin (phaP), and the regulator protein (phaR) was previously identified in Rhodobacter sphaeroides FJ1 (R. sphaeroides FJ1). In this study, we investigated the role of the PhaR protein on the expression of the pha genes. Immunoblot analysis revealed that the expressions of phaP, phaZ and phaR genes in wild-type cells of R. sphaeroides FJ1 are repressed during the active growth phase, with the exception of phaC. A phaR deletion mutant of R. sphaeroides FJ1 was constructed, and the basal level of phaP and phaZ expression in this mutant was markedly increased. Electrophoretic mobility shift assays demonstrated that PhaR binds to the promoter region of phaP as well as those of phaR and phaZ. These results suggest that the PhaR protein is a repressor of phaP, phaR, and phaZ genes in R. sphaeroides FJ1.     

Prediction of response and adverse drug reaction of pemetrexed plus platinum-based chemotherapy in lung adenocarcinoma by serum metabolomic profiling

BackgroundPemetrexed plus platinum doublet chemotherapy regimen remains to be the standard first-line treatment for lung adenocarcinoma patients. However, few biomarkers can be used to identify potential beneficiaries with maximal efficacy and minimal toxicity. This study aimed to explore potential biomarker models predictive of efficacy and toxicity after pemetrexed plus platinum chemotherapy based on metabolomics profiling.MethodsA total of 144 patients who received at least two cycles of pemetrexed plus platinum chemotherapy were enroled in the study. Serum samples were collected before initial treatment to perform metabolomics profiling analysis. Logistic regression analysis was performed to establish prediction models.Results157 metabolites were found to be differentially expressed between the response group and the nonresponse group. A panel of Phosphatidylserine 20:4/20:1, Sphingomyelin d18:1/18:0, and Phosphatidic Acid 18:1/20:0 could predict pemetrexed and platinum chemotherapy response with an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.7968. 76 metabolites were associated with hematological toxicity of pemetrexed plus platinum chemotherapy. A panel incorporating triglyceride 14:0/22:3/22:5, 3-(3-Hydroxyphenyl) Propionate Acid, and Carnitine C18:0 was the best predictive ability of hematological toxicity with an AUROC of 0.7954. 54 differential expressed metabolites were found to be associated with hepatotoxicity of pemetrexed plus platinum chemotherapy. A model incorporating stearidonic acid, Thromboxane B3, l-Homocitrulline, and phosphoinositide 20:3/18:0 showed the best predictive ability of hepatotoxicity with an AUROC of 0.8186.ConclusionsThis study established effective and convenient models that can predict the efficacy and toxicity of pemetrexed plus platinum chemotherapy in lung adenocarcinoma patients before treatment delivery.