Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice.

AIMS: Perioperative neurocognitive disorders (PND) are associated with cognitive impairment in the preoperative or postoperative period, and neuroinflammation is thought to be the most important mechanisms especially during the postoperative period. The GABAergic system is easily disrupted by neuroinflammation. This study investigated the impact of the GABAergic system on PND after anesthesia and surgery. METHODS: An animal model of laparotomy with inhalation anesthesia in 16-month-old mice was addressed. Effects of the GABAergic system were assessed using biochemical analysis. Pharmacological blocking of α5GABAA Rs or P38 mitogen-activated protein kinase (MAPK) were applied to investigate the effects of the GABAergic system. RESULTS: After laparotomy, the hippocampus-dependent memory and long-term potentiation were impaired, the levels of IL-6, IL-1ß and TNF-α up-regulated in the hippocampus, the concentration of GABA decreased, and the protein levels of the surface α5GABAA Rs up-regulated. Pharmacological blocking of α5GABAA Rs with L655,708 alleviated laparotomy induced cognitive deficits. Further studies found that the P38 MAPK signaling pathway was involved and pharmacological blocking with SB203,580 alleviated memory dysfunctions. CONCLUSIONS: Anesthesia and surgery caused neuroinflammation in the hippocampus, which consequently disrupted the GABAergic system, increased the expressions of surface α5GABAA Rs especially through the P38 MAPK signaling pathway, and eventually led to hippocampus-dependent memory dysfunctions.

Dezocine regulates the malignant potential and aerobic glycolysis of liver cancer targeting Akt1/GSK-3ß pathway.

BACKGROUND: Due to the "ceiling effect" of respiratory depression and the non-addictiveness, the consumption of dezocine is increasing quickly in the cancer surgery perioperative period for security and comfort reasons in China. Former studies find dezocine inhibits the norepinephrine transporters (NET) and serotonin transporters (SERT) and sigma-1opioid receptors. Given the complexity of the molecular mechanism, the effect of dezocine on tumor cells need to be studied. In this study, we investigated the effect of dezocine on HepG2 and Hep 3B liver cancer cell lines growth and glycolysis, and the molecular mechanisms behind. METHODS: HepG2 and Hep 3B cells viability and migration were measured by CCK8, Wound healing and transwell assay, Extracellular acidification rate (ECAR) was used to index the aerobic glycolysis of liver cancer cells and western blot analysis showed protein expression levels in the cells. SC79, an agonist of Akt, and the siRNA silence of Akt1 aimed to regulate Akt1 activity and expression in the reverse experiments. RESULTS: Dezocine played opposite roles in HepG2 and Hep 3B cells viability and migration in a concentration-dependent manner (P<0.01). Dezocine has diverse effects on aerobic glycolysis and adjusts the serine/threonine kinase 1 (Akt1)-glycogen synthase kinase-3ß (GSK-3ß) pathway. The effects of SC79 and the siRNA silence of Akt1 could reverse the effects of dezocine on HepG2 and Hep 3B cells. CONCLUSIONS: As an analgesic drug widely used in clinical practice, dezocine play reversed roles on HepG2 and Hep 3B cells viability and migration targeting Akt1/GSK-3ß pathway then the glycolysis in a concentration-dependent manner.

PGE2-EP3 signaling exacerbates hippocampus-dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity-related proteins in aged mice.

AIM: Multifactors contribute to the development of postoperative cognitive dysfunction (POCD), of which the most important mechanism is neuroinflammation. Prostaglandin E2 (PGE2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE2 and its receptors signaling pathway were involved in the pathophysiology of POCD. METHODS: Sixteen-month old male C57BL/6J mice were exposed to laparotomy. Cognitive function was evaluated by fear conditioning test. The levels of PGE2 and its 4 distinct receptors (EP1-4) were assessed by biochemical analysis. Pharmacological or genetic methods were further applied to investigate the role of the specific PGE2 receptors. RESULTS: Here, we found that the transcription and translation level of the EP3 receptor in hippocampus increased remarkably, but not EP1, EP2, or EP4. Immunofluorescence results showed EP3 positive cells in the hippocampal CA1 region were mainly neurons. Furthermore, pharmacological blocking or genetic suppression of EP3 could alleviate surgery-induced hippocampus-dependent memory deficits and rescued the expression of plasticity-related proteins, including cAMP response element-binding protein (CREB), activity-regulated cytoskeletal-associated protein (Arc), and brain-derived neurotrophic factor (BDNF) in hippocampus. CONCLUSION: This study showed that PGE2-EP3 signaling pathway was involved in the progression of POCD and identified EP3 receptor as a promising treatment target.

[Photocatalytic degradation of acetamiprid by TiO2 and Xe lamp: kinetics and degradation intermediates].

Photocatalytic degradation kinetics of acetamiprid was studied by both of single-variable-at-a-time (SVAT) and central composite design (CCD) experiments based on four factors, such as catalyst dosages, substrate concentration, temperature and pH values. The results indicated that degradation of acetamiprid followed pseudo first-order kinetics by Langmuir-Hinshelwood model, increased with the increasing of temperature and the decreasing of substrate concentration. The photocatalytic degradation kinetic rate of acetamiprid was low in acid solutions, while high in weak acidic and alkaline solutions. After studying the synergistic effects of these four classic parameters, the optimal experiment conditions for photocatalytic degradation of acetamiprid were obtained as follows: TiO2 at 2.30 g x L(-1), initial acetamiprid concentration of 90.0 µmol x L(-1), temperature of 37.5 degrees C and pH value at 5.0. Lastly, 7 degradation intermediates of acetamiprid were detected during photocatalytic process by HPLC, and 6 of them exhibited more polar than the parent molecule.

Development of a one-step immunocapture real-time RT-PCR assay for detection of tobacco mosaic virus in soil.

Tobacco mosaic virus (TMV) causes significant losses in many economically important crops. Contaminated soils may play roles as reservoirs and sources of transmission for TMV. In this study we report the development of an immunocapture real-time RT-PCR (IC-real-time RT-PCR) assay for direct detection of TMV in soils without RNA isolation. A series of TMV infected leaf sap dilutions of 1:101, 1:102, 1:103, 1:104, 1:105 and 1:106 (w/v, g/mL) were added to one gram of soil. The reactivity of DAS-ELISA and conventional RT-PCR was in the range of 1:102 and 1:103 dilution in TMV-infested soils, respectively. Meanwhile, the detection limit of IC-real-time RT-PCR sensitivity was up to 1:106 dilution. However, in plant sap infected by TMV, both IC-real-time RT-PCR and real-time RT-PCR were up to 1:106 dilution, DAS-ELISA could detect at least 1:103 dilution. IC-real-time RT-PCR method can use either plant sample extracts or cultivated soils, and show higher sensitivity than RT-PCR and DAS-ELISA for detection of TMV in soils. Therefore, the proposed IC-real-time RT-PCR assay provides an alternative for quick and very sensitive detection of TMV in soils, with the advantage of not requiring a concentration or RNA purification steps while still allowing detection of TMV for disease control.

Identification of the critical structural determinants of the EF-hand domain arrangements in calcium binding proteins.

EF-hand calcium binding proteins (CaBPs) share strong sequence homology, but exhibit great diversity in structure and function. Thus although calmodulin (CaM) and calcineurin B (CNB) both consist of four EF hands, their domain arrangements are quite distinct. CaM and the CaM-like proteins are characterized by an extended architecture, whereas CNB and the CNB-like proteins have a more compact form. In this study, we performed structural alignments and molecular dynamics (MD) simulations on 3 CaM-like proteins and 6 CNB-like proteins, and quantified their distinct structural and dynamical features in an effort to establish how their sequences specify their structures and dynamics. Alignments of the EF2-EF3 region of these proteins revealed that several residues (not restricted to the linker between the EF2 and EF3 motifs) differed between the two groups of proteins. A customized inverse folding approach followed by structural assessments and MD simulations established the critical role of these residues in determining the structure of the proteins. Identification of the critical determinants of the two different EF-hand domain arrangements and the distinct dynamical features relevant to their respective functions provides insight into the relationships between sequence, structure, dynamics and function among these EF-hand CaBPs.