Neuronal lack of PDE7a disrupted working memory, spatial learning, and memory but facilitated cued fear memory in mice.

BACKGROUND: PDEs regulate cAMP levels which is critical for PKA activity-dependent activation of CREB-mediated transcription in learning and memory. Inhibitors of PDEs like PDE4 and Pde7 improve learning and memory in rodents. However, the role of PDE7 in cognition or learning and memory has not been reported yet. METHODS: Therefore, we aimed to explore the cognitive effects of a PDE7 subtype, PDE7a, using combined pharmacological and genetic approaches. RESULTS: PDE7a-nko mice showed deficient working memory, impaired novel object recognition, deficient spatial learning & memory, and contextual fear memory, contrary to enhanced cued fear memory, highlighting the potential opposite role of PDE7a in the hippocampal neurons. Further, pharmacological inhibition of PDE7 by AGF2.20 selectively strengthens cued fear memory in C57BL/6 J mice, decreasing its extinction but did not affect cognitive processes assessed in other behavioral tests. The further biochemical analysis detected deficient cAMP in neural cell culture with genetic excision of the PDE7a gene, as well as in the hippocampus of PDE7a-nko mice in vivo. Importantly, we found overexpression of PKA-R and the reduced level of pPKA-C in the hippocampus of PDE7a-nko mice, suggesting a novel mechanism of the cAMP regulation by PDE7a. Consequently, the decreased phosphorylation of CREB, CAMKII, eif2a, ERK, and AMPK, and reduced total level of NR2A have been found in the brain of PDE7a-nko animals. Notably, genetic excision of PDE7a in neurons was not able to change the expression of NR2B, BDNF, synapsin1, synaptophysin, or snap25. CONCLUSION: Altogether, our current findings demonstrated, for the first time, the role of PDE7a in cognitive processes. Future studies will untangle PDE7a-dependent neurobiological and molecular-cellular mechanisms related to cAMP-associated disorders.

Cytotoxic effects of extracts and isolated compounds from Ifloga spicata (forssk.) sch. bip against HepG-2 cancer cell line: Supported by ADMET analysis and molecular docking.

The purpose of this study was to determine the anticancer potential of Ifloga spicata (I. spicata) against HepG-2 cell line. To assess I. spicata cytoxicity, brine shrimp lethality and MTT assays were performed. In the brine shrimp bioassay, the ethyl acetate fraction had a significant impact with an IC50 of 10 µg/ml. The ethyl acetate and chloroform fractions inhibited HepG-2 cell line effectively (IC50 values 5.54 and 6.52 µg/ml, respectively). The isolated compound, heptadecyl benzoate inhibited growth significantly (IC50, 8.92 µg/ml) while methyl dihydroxybenzoate had modest activity (25.66 µg/ml) against the cell line. Both compounds displayed acceptable pharmacokinetic parameters in the ADME study. In the docking study, the methyl dihydroxybenzoate was involved in two hydrogen bonds with two different residues Thr830 and Asp831. The heptadecyl benzoate carbonyl oxygen exhibited a single hydrogen bond with Lys692. Both showed good interactions with the active site of the (EGFR) tyrosine kinase. Our findings suggest that I. spicata might be a viable source of anticancer natural agents. This discovery raises the prospect of the future development of a new medication for the treatment of liver cancer.

Clinical features of full-term neonates with respiratory syncytial virus pneumonia / 中国小儿急救医学

Objective To explore the clinical features of respiratory syncytial virus(RSV) pneumonia in full-term neonatal patients.Methods All 422 full-term newborns diagnosed as pneumonia in NICU of Shenzhen Children's Hospital during January 2014 to January 2015 were included in this study.They had been detected for RSV in the way of direct immunofluorescence assay.According to the detection results, they were divided into RSV positive group and RSV negative group, the clinical data in two groups were analyzed.Results Forty-five cases were RSV positive,377 cases were RSV negative.The proportion of breast feeding was 42.22％ vs.65.25％ ,the proportion of cesarean section was 20.00％ vs.76.12％ in two groups,there were significant differences between the two groups.Hospitalization time, birth weight, gestational age, the age of admission showed no difference between two groups.The incidencs of cough (100％), shormess of breath (88.89％), three depressions (48.89 ％), fine rales (66.67 ％), wheezing (22.22％) in RSV positive group were higher than those in the RSV negative group(84.88％ ,42.44％, 13.26％, 13.53％ ,3.98％ respectively), there were significant differences between the two groups.The incidences of fever, saliva, nasal showed no significant difference between the two groups.There was significant difference in the X-ray chest film performance between two groups,RSV positive group was more emhrysema(71.11％ vs.6.9％) ,and less patch shadow(88.89％ vs.93.10％).The laboratory examination of blood routine test, C-reactive protein,respiratory failure, the positive rate of sputum culture, pneumothorax, pleural effusion were without differences.Conclusion RSV is an important pathogen of full-term neonates with infectious pneumonia.Breastfeeding and eutocia can reduce the incidence of RSV infection.Cough, shortness of breath, pulmonary rales, and emphysema in X-ray were common in RSV pneumonia.

Olig1 gene expression in brain tissue of newborn rat of periventricular leukomalacia and the relation with remyelination / 中国小儿急救医学

Objective To determine Oligl transcription factor expression in periventricular tissue of day 2 newborn rat of periventricular leukomalacia (PVL) and to explore the relation with remyelination.Methods PVL newborn rat model was successfully established through bilateral common carotid artery ligation,followed by 8% oxygen exposure for 30 min. On day 0,day 7 and day 14 after operation,Oligl expression was examined through in situ hybridization, oligodendrocyte precursor cells and oligodendrocytes were detected via immunohistochemistry method and mRNA levels of MBP, PLP, MAG in control and PVL group were examined with quantitative real-time PCR. Results Oligl positive cells of control group were 115 ± 15/mm2. On day 0 and day 7 after operation,oligl positive cells were 72 ± 20/mm2and 75 ± 12/mm2 ,and there was significant difference as compared with control group (P both ＜ 0. 05), however the oligl positive cells on day 14 after operation(146 ± 1 1/mm2) significantly increased with comparison to control group (P ＜0. 05). Compared to control group, GST-Ⅱ positive oligodendrocytes and O4 positive oligodendroglial progenitor cells of PVL group were significantly decreased on day 0, day 7 after operation (P both ＜ 0. 05), and these cells both increased on day 14 after operation ,however there was no difference as compared with control group (P ＞ 0. 05). Compared to control group, mRNA levels of MBP, PLP, MAG all significantly decreased on day 0,day 7 after operation(P all ＜ 0. 05), and these levels slightly increased on day 14 after operation (P ＞ 0. 05). Conclusion Oligl transcription factor may be essential in the remyelination and repair of myelin in PVL.