Hsa_circ_0001658 accelerates the progression of colorectal cancer through miR-590-5p/METTL3 regulatory axis.

BACKGROUND: As reported, multiple circular RNAs (circRNAs) interfere with colorectal cancer (CRC) progression. Here, circRNA_0001658 (circ_0001658) is focused on studying how it works in CRC. AIM: Clarify the expression pattern, biological function, and underlying mechanism of circ_0001658 of CRC tumorigenesis. METHODS: In CRC-related chip data retrieved using the database named Gene Expression Omnibus, different expressions of circRNAs between CRC and normal tissue samples were identified. Quantitative Real-time PCR and Western blot ensured the analysis on circ_0001658, microRNA-590-5P (miR-590-5p), and methyltransferase-like 3 (METTL3) mRNA expressions in tissues and cells. Cell counting kit-8 and flow cytometry were used to detect cell proliferation, apoptosis and migration. The targeting relations between circ_0001658, miR-590-5p, and METTL3 mRNA 3'-untranslated region were under the verification of bioinformatics prediction and dual luciferase-based reporter gene assays. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were employed on the downstream targets of miR-590-5p using the Database for Annotation, Visualization and Integrated Discovery database. RESULTS: Circ_0001658 and METTL3 mRNA was elevated in CRC tissues and cells, whereas miR-590-5p was decreased. Circ_0001658 overexpression promoted the proliferation of HT29 cells, inhibited apoptosis, and accelerated the cell cycle. In SW480 cells, knocking down circ_0001658 had the opposite effect. Circ_0001658 could specifically bind to miR-590-5p and negatively modulate its expressions; METTL3 is a miR-590-5p target that can be positively regulated by circ 0001658. Circ 0001658 was inversely associated with miR-590-5p expression while positively with METTL3 expressions. CONCLUSION: Circ_0001658 regulates the miR-590-5p/METTL 3-axis to increase CRC cell growth and decrease apoptosis.

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies.

Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy and safety of the perioperative application of ketamine on postoperative depression remains uncertain. We performed a meta-analysis to determine the effect of perioperative intravenous administration of ketamine on postoperative depression. Randomized controlled trials comparing ketamine with placebo in patients were included. Primary outcome was postoperative depression scores. Secondary outcomes included postoperative visual analog scale (VAS) scores for pain and adverse effects associated with ketamine. Fifteen studies with 1697 patients receiving ketamine and 1462 controls were enrolled. Compared with the controls, the ketamine group showed a reduction in postoperative depression scores, by a standardized mean difference (SMD) of -0.97, 95% confidence interval [CI, -1.27, -0.66], P < 0.001, I2 = 72% on postoperative day (POD) 1; SMD-0.65, 95% CI [-1.12, -0.17], P < 0.001, I2 = 94% on POD 3; SMD-0.30, 95% CI [-0.45, -0.14], P < 0.001, I2 = 0% on POD 7; and SMD-0.25, 95% CI [-0.38, -0.11], P < 0.001, I2 = 59% over the long term. Ketamine reduced VAS pain scores on POD 1 (SMD-0.93, 95% CI [-1.58, -0.29], P = 0.005, I2 = 97%), but no significant difference was found between the two groups on PODs 3 and 7 or over the long term. However, ketamine administration distinctly increased the risk of adverse effects, including nausea and vomiting (risk ratio [RR] 1.40, 95% CI [1.12, 1.75], P = 0.003, I2 = 30%), headache (RR 2.47, 95% CI [1.41, 4.32], P = 0.002, I2 = 19%), hallucination (RR 15.35, 95% CI [6.24, 37.34], P < 0.001, I2 = 89%), and dizziness (RR 3.48, 95% CI [2.68, 4.50], P < 0.001, I2 = 89%) compared with the controls. In conclusion, perioperative application of ketamine reduces postoperative depression and pain scores with increased risk of adverse effects.

A role of GABAA receptor α1 subunit in the hippocampus for rapid-acting antidepressant-like effects of ketamine.

Ketamine can produce rapid-acting antidepressant effects in treatment-resistant patients with depression. Although alterations in glutamatergic and GABAergic neurotransmission in the brain play a role in depression, the precise molecular mechanisms in these neurotransmission underlying ketamine's antidepressant actions remain largely unknown. Mice exposed to FSS (forced swimming stress) showed depression-like behavior and decreased levels of GABA (γ-aminobutyric acid), but not glutamate, in the hippocampus. Ketamine increased GABA levels and decreased glutamate levels in the hippocampus of mice exposed to FSS. There was a correlation between GABA levels and depression-like behavior. Furthermore, ketamine increased the levels of enzymes and transporters on the GABAergic neurons (SAT1, GAD67, GAD65, VGAT and GAT1) and astrocytes (EAAT2 and GAT3), without affecting the levels of enzymes and transporters (SAT2, VGluT1 and GABAAR γ2) on glutamatergic neurons. Moreover, ketamine caused a decreased expression of GABAAR α1 subunit, which was specifically expressed on GABAergic neurons and astrocytes, an increased GABA synthesis and metabolism in GABAergic neurons, a plasticity change in astrocytes, and an increase in ATP (adenosine triphosphate) contents. Finally, GABAAR antagonist bicuculline or ATP exerted a rapid antidepressant-like effect whereas pretreatment with GABAAR agonist muscimol blocked the antidepressant-like effects of ketamine. In addition, pharmacological activation and inhibition of GABAAR modulated the synthesis and metabolism of GABA, and the plasticity of astrocytes in the hippocampus. The present data suggest that ketamine could increase GABA synthesis and astrocyte plasticity through downregulation of GABAAR α1, increases in GABA, and conversion of GABA into ATP, resulting in a rapid-acting antidepressant-like action. This article is part of the Special Issue on 'Ketamine and its Metabolites'.

Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A Randomized Clinical Trial.

Importance: Postoperative sleep disturbance (PSD) is common in patients after surgery. Objective: To examine the effect of intraoperative esketamine infusion on the incidence of PSD in patients who underwent gynecological laparoscopic surgery. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted from August 2021 to April 2022 in the First Affiliated Hospital of Zhengzhou University in China. Participants included patients aged 18 to 65 years with an American Society of Anesthesiologist Physical Status classification of I to III (with I indicating a healthy patient, II a patient with mild systemic disease, and III a patient with severe systemic disease) who underwent gynecological laparoscopic surgery. Patients were randomly assigned to either the esketamine group or control group. Data were analyzed using the per protocol principle. Interventions: Patients in the esketamine group received a continuous infusion of esketamine, 0.3 mg/kg/h, intraoperatively. Patients in the control group received an equivalent volume of saline. Main Outcomes and Measures: The primary outcome was the incidence of PSD on postoperative days (PODs) 1 and 3. Postoperative sleep disturbance was defined as a numeric rating scale score of 6 or higher or an Athens Insomnia Scale score of 6 points or higher. The secondary outcomes included postoperative anxiety and depression scores using the Hospital Anxiety and Depression Scale, postoperative pain using the visual analog scale, postoperative hydromorphone consumption, and risk factors associated with PSD. Results: A total of 183 female patients were randomized to the control group (n = 91; median [IQR] age, 45 [35-49] years) and the esketamine group (n = 92; median [IQR] age, 43 [32-49] years). The incidence of PSD in the esketamine group was significantly lower than in the control group on POD 1 (22.8% vs 44.0%; odds ratio [OR], 0.38 [95% CI, 0.20-0.72]; P = .002) and POD 3 (7.6% vs 19.8%; OR, 0.33 [95% CI, 0.13-0.84]; P = .02). There were no differences in postoperative depression and anxiety scores between the 2 groups. Postoperative hydromorphone consumption in the first 24 hours (3.0 [range, 2.8-3.3] mg vs 3.2 [range, 2.9-3.4] mg; P = .04) and pain scores on movement (3 [3-4] vs 4 [3-5] points; P < .001) were significantly lower in the esketamine group than in the control group. On multivariable logistic regression, preoperative depression (OR, 1.31; 95% CI, 1.01-1.70) and anxiety (OR, 1.67; 95% CI, 1.04-1.80) scores, duration of anesthesia (OR, 1.04; 95% CI, 1.00-1.08), and postoperative pain score (OR, 1.92; 95% CI, 1.24-2.96) were identified as risk factors associated with PSD. Conclusions and Relevance: Results of this trial showed the prophylactic effect of intraoperative esketamine infusion on the incidence of PSD in patients who underwent gynecological laparoscopic surgery. Further studies are needed to confirm these results. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100048587.

Effects of bromate on life history parameters, swimming speed and antioxidant biomarkers in Brachionus calyciflorus.

The baking industries and disinfection of tap water released a considerable amount of bromate into surface water, which has been reported as a carcinogenic compound to mammals. Rotifers play an important role in freshwater ecosystems and are model organisms to assess environmental contamination. In the present study, the effects of different concentrations (0.001, 0.01, 0.1, 1, 10, 100 and 200 mg/L) of bromate on the life-table and population growth parameters were investigated in the rotifer Brachionus calyciflorus. The results showed that the 24-h LC50 of bromate to B. calyciflorus was 365.29 mg/L (95%Cl: 290.37-480.24). Treatments with 0.01, 10 and 200 mg/L bromate shorten the reproductive period. High levels of bromate (100 and 200 mg/L) significantly decreased net reproductive rate, intrinsic rate of population increase, life span, mictic rate of B. calyciflorus. To investigate the underlying mechanisms, swimming speed and antioxidative biomarkers were compared between bromate treatments and the control. The results showed that glutathione (GSH) and malondialdehyde (MDA) contents, total superoxide dismutase (T-SOD) and peroxidase (POD) activities decreased significantly in response to bromate exposure and the reasons required further investigation. Treatments with 0.001-200 mg/L bromate all significantly reduced swimming linear speed to rotifer larvae and treatments with 100-200 mg/L bromate significantly suppressed the swimming linear speed of adult rotifer. These changes would reduce filtration of algal food and could explain the decreased survival and reproduction. Overall, bromate may not show acute toxicity to rotifers, but still have potential adverse effects on rotifer behavior, which may then influence the community structure in aquatic ecosystems.

Improving native human sperm freezing protection by using a modified vitrification method.

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.

Environmental enrichment improves pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain: role of NPAS4.

Patients suffering from neuropathic pain have a higher incidence of depression and cognitive decline. Although environment enrichment (EE) may be effective in the treatment of neuropathic pain, the precise mechanisms underlying its actions remain determined. The aim of the study was to examine the molecular mechanisms underlying the EE's beneficial effects in mice with neuropathic pain. EE attenuated the pain threshold reduction, depression-like phenotype, and memory deficit in mice after chronic constriction injury (CCI). Furthermore, EE attenuated decreased neurogenesis and increased inflammation in the hippocampus of mice with neuropathic pain after CCI. Moreover, the suppression of adult hippocampal neurogenesis by temozolomide antagonized the beneficial effects of EE on depression-like phenotype and cognitive deficit in the mice with neuropathic pain. In addition, lipopolysaccharide-induced increase in tumor necrosis factor-α (TNF-α) in the hippocampus antagonized the beneficial effects of EE for these behavioral abnormalities in mice with neuropathic pain. Knock-down of NPAS4 (neuronal PAS domain protein 4) in the hippocampus by lentivirus targeting NPAS4 blocked these beneficial effects of EE in the mice with neuropathic pain. These all findings suggest that hippocampal NPAS4 plays a key role in the beneficial effects of EE on the pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain. Therefore, it is likely that NPAS4 would be a new therapeutic target for perceptional, affective, and cognitive dimensions in patients with chronic pain.

Environmental enrichment improves long-term memory impairment and aberrant synaptic plasticity by BDNF/TrkB signaling in nerve-injured mice.

Nerve injury can induce memory impairment in mice. The aim of this research is to study the effect of environmental enrichment (EE) on long-term memory impairment in nerve-injured mice and the underlying mechanisms. Adult male C57BL/6 mice were received sham or chronic constriction injury (CCI) operation and reared in a standard environment (SE) or EE for 4 weeks after the operation. The pain threshold, long-term memory, expression of brain-derived neurotrophic factor (BDNF) and synaptic plasticity in hippocampus were determined. The results showed that CCI can induce the reduction in the mechanical and thermal pain thresholds, which were accompanied by long-term memory deficits in mice. CCI also induced the reduction of BDNF expression and synaptic plasticity impairments in the hippocampus, as represented by the dendritic spine density and postsynaptic density protein (PSD)-95 reduction, and long-term potential (LTP) dysfunction. Notably, EE can ameliorate the pain threshold and BDNF reduction, long-term memory deficits, and synaptic plasticity impairments in nerve-injured mice. However, the tropomyosin receptor kinase (Trk) B antagonist, ANA-12, blocked the EE-induced improvement in the long-term memory and synaptic plasticity impairment in nerve-injured mice. In conclusion, EE improved the pain threshold reduction, long-term memory and synaptic plasticity deficits in nerve-injured mice; BDNF / Trk B signaling may contribute to the relief of long-term memory and synaptic plasticity deficits induced by EE in nerve-injured mice.

Cellular prion protein is involved in decidualization of mouse uterus.

Prion protein (PrP) is encoded by a single copy gene Prnp in many cell and tissue types. PrP is very famous for its infectious conformers (PrPSC) resulting in transmissible spongiform encephalopathies. At present, physiological functions of its cellular isoform (PrPC) remain ambiguous. Although PrPC expression has been found in uterus, whether it functions in maternal-fetal dialogue during early pregnant is unknown. In this study, we examined PrPC mRNA and protein in the uterus of peri-implantation mice, and found that they were expressed with a spatiotemporal dynamic pattern. Interestingly, PrPC was significantly increased in the decidual zones around the implanting embryos at the implantation window stage. To further demonstrate that PrPC is involved in the decidualization of mouse uterus during embryo implantation, we constructed the artificial decidualization models and the delayed implantation models. Once the pseudopregnant mice were artificially induced to decidualization, the PrPC expression then increased significantly in the decidua zone. And also, if the delayed implantation embryos were allowed to implant, PrPC protein was also simultaneously improved in stromal cells surrounding the implanting embryos. Moreover, PrPC expression can be inhibited by progesterone but upregulated by estrogen in mouse uterus. These results suggest that PrPC may play an important role in embryo implantation and decidualization.

Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine.

Although pain is frequently accompanied with depression, little is known about the risk factors contributing to individual differences to the comorbidity of pain and depression. In this study, we examined whether cytokines and brain-derived neurotrophic factor (BDNF) might contribute to the individual differences in the development of neuropathic pain-induced depression. Rats were randomly subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups by the data from depression-related behavioral tests. Rats with depression-like phenotype displayed higher levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1ß, IL-6) as well as imbalance of pro/anti-inflammatory cytokines compared with rats without depression-like phenotype and sham-operated rats. Levels of BDNF in the prefrontal cortex of rats with depression-like phenotype were lower than those of rats without depression-like phenotype and sham-operated rats. A single dose of ketamine ameliorated depression-like behaviors in the rats with depression-like phenotype. Interestingly, higher serum levels of IL-1ß and IL-6 in the rat with depression-like phenotype were normalized after a single dose of ketamine. These findings suggest that alterations in the inflammatory cytokines and BDNF might contribute to neuropathic pain-induced depression, and that serum cytokines may be predictable biomarkers for ketamine's antidepressant actions.

NOX2 Mediated-Parvalbumin Interneuron Loss Might Contribute to Anxiety-Like and Enhanced Fear Learning Behavior in a Rat Model of Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, yet the precise mechanisms underlying PTSD remains largely to be determined. Using an animal model of PTSD induced by a single prolonged stress (SPS), we assessed the role of hippocampal nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and parvalbumin (PV) interneurons in the development of PTSD symptoms. In the present study, behavioral tests were performed by the open field (day 13 after SPS) and fear conditioning tests (days 13 and 14 after SPS). For the interventional study, rats were chronically treated with a NADPH oxidase inhibitor apocynin either by early or delayed administration. The levels of tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6, IL-10, malondialdehyde, superoxide dismutase, NOX2, 4-hydroxynonenal, and PV in the hippocampus were measured at the indicated time points. In the present study, we showed that SPS rats displayed anxiety-like and enhanced fear learning behavior, which was accompanied by the increased expressions of malondialdehyde, IL-6, NOX2, 4-hydroxynonenal, and decreased PV expression. Notably, early but not delayed treatment with apocynin reversed all these abnormalities after SPS. In conclusion, our results provided evidence that NOX2 activation in the hippocampus, at least in part, contributes to oxidative stress and neuroinflammation, which further results in PV interneuron loss and consequent PTSD symptoms in a rat model of PTSD induced by SPS.

Interaction between tryptophan-Sm(III) complex and DNA with the use of a acridine orange dye fluorophor probe.

The interaction of the Trp-Sm(III) complex with herring sperm DNA (hs-DNA) was investigated with the use of acridine orange (AO) dye as a spectral probe for UV-vis spectrophotometry and fluorescence spectroscopy. The results showed that the both the Trp-Sm(III) complex and the AO molecule could intercalate into the double helix of the DNA. The Sm(III)-(Trp)3 complex was stabilized by intercalation into the DNA with binding constants: K(Ó¨)25°C = 7.14 × 10(5) L·mol(-1) and K(Ó¨) 37°C = 5.28 × 10(4) L·mol(-1), and it could displace the AO dye from the AO-DNA complex in a competitive reaction. Computation of the thermodynamic functions demonstrates that Δr Hm (Ó¨) is the primary driving power of the interaction between the Sm(III)(Trp)3 complex and the DNA. The results from Scatchard and viscometry methods suggested that the interaction mode between the Sm(III)(Trp)3 complex and the hs-DNA is groove binding and weak intercalation binding.

Environmental Enrichment Ameliorates Neonatal Sevoflurane Exposure-Induced Cognitive and Synaptic Plasticity Impairments.

Early exposure to sevoflurane, an inhalation anesthetic, induces neurodegeneration in the developing brain and subsequent long-term neurobehavioral abnormalities. Here, we investigated whether an enriched environment could mitigate neonatal sevoflurane exposure-induced long-term cognitive and synaptic plasticity impairments. Male C57BL/6 mice were exposed to 3 % sevoflurane 2 h daily for 3 days from postnatal day 6 (P6) to P8. The exposed mice were randomly allocated to an enriched environment for 2 h daily between P8 and P42 or to a standard environment. Their behavior and cognition were assessed using open field (P35) and fear conditioning tests (P41-P42). Hematoxylin-eosin staining was used to study morphological changes in pyramidal neurons of hippocampal CA1 and CA3 regions. Synaptic plasticity alternations were assessed using western blotting, Golgi staining, and electrophysiological recording. We found that sevoflurane-exposed mice housed in a standard environment exhibited a reduced freezing response in the contextual test, decreased number of dendritic spines on pyramidal neurons and synaptic plasticity-related proteins in the hippocampus, and impaired long-term potentiation. However, in an enriched environment, some of these abnormities induced by repeated sevoflurane exposure. In conclusion, neonatal sevoflurane exposure-induced cognitive and synaptic plasticity impairments are ameliorated by an enriched environment.

Downregulation of neuregulin 1-ErbB4 signaling in parvalbumin interneurons in the rat brain may contribute to the antidepressant properties of ketamine.

Increasing evidence underscores the strong, rapid, and sustained antidepressant properties of ketamine with a good tolerability profile in patients with depression; however, the underlying mechanisms are not fully elucidated. Neuregulin 1 (NRG1) is a bipolar disorder susceptibility gene and a biomarker of major depressive disorder, which regulates pyramidal neuron activity via ErbB4 in parvalbumin interneurons. Moreover, NRG1-ErbB4 signaling is reported to play a key role in the modulation of synaptic plasticity through regulating the neurotransmission. We therefore hypothesized that hypofunction of NRG1-ErbB4 signaling in parvalbumin interneurons is involved in the process of ketamine exerting rapid antidepressant actions in rats subjected to the forced swimming test (FST). The results showed that ketamine reduced the immobility time and latency to feed of rats receiving the FST, downregulated the levels of NRG1, phosphorylated ErbB4 (p-ErbB4), parvalbumin, 67-kDA isoform of glutamic acid decarboxylase (GAD67), gamma-aminobutyric acid (GABA), and upregulated the levels of glutamate in the rat prefrontal cortex and hippocampus. Pretreatment with NRG1 abolished both ketamine's antidepressant effects and ketamine-induced reduction in p-ErbB4, parvalbumin, GAD67, and GABA levels and increase in glutamate levels. These results suggest that the downregulation of NRG1-ErbB4 signaling in parvalbumin interneurons in the rat brain may be a mechanism underlying ketamine's antidepressant properties.

Spectroscopic studies on the interaction mechanisms of safranin T with herring sperm DNA using acridine orange as a fluorescence probe.

Under the condition of physiological pH environment (pH = 7.40), the interactions of safranin T (ST) with herring sperm DNA were studied by means of spectral methods using acridine orange (AO) as a fluorescence probe. The spectroscopic characteristics of DNA-AO in the case of ST (along with the increase of concentration) were observed in an aqueous medium. The binding constants for ST stranded DNA and competitive bindings of ST interacting with DNA-AO systems were examined by fluorescence spectra, and the binding mechanism of ST with DNA was researched via viscosity measurements. All the testimony manifested that bonding modes between ST and DNA were evidenced to be intercalative binding and electrostatic binding, and the combining constant of ST with DNA was obtained. The binding of ST to DNA was driven by entropy and enthalpy through the calculated thermodynamic parameters (Δr Hm (Ó¨), Δr Sm and Δr Gm (Ó¨)).

Resveratrol pretreatment attenuates the isoflurane-induced cognitive impairment through its anti-inflammation and -apoptosis actions in aged mice.

Although the underlying mechanisms of isoflurane-induced cognitive impairments remain largely to be determined, neuronal inflammation and apoptosis are thought to be major contributors. Resveratrol is a naturally available herbal compound for the treatment of inflammatory and neurodegenerative diseases. We therefore aimed to investigate the effects of resveratrol on the isoflurane-induced cognitive impairments and the associated hippocampal inflammation responses and neuronal apoptosis in the aged mice. Fifteen-month-old male C57BL/6 mice received 2 h of 1.5 % isoflurane or oxygen exposure 24 h after the intraperitoneal injection of resveratrol or saline daily for 7 consecutive days. Here, we showed that the isoflurane anesthesia decreased the freezing time to context significantly at 48 h after the isoflurane exposure in the fear conditioning test. The hippocampal levels of IL-1ß, TNF-α, NLRP3, cleaved caspase-3, and Bax increased significantly while the hippocampal levels of IkBα and Bcl-2 decreased significantly at 6 and/or 48 h after the isoflurane anesthesia. All these effects induced by isoflurane were attenuated by resveratrol pretreatment. However, the isoflurane anesthesia had no significant effect on the hippocampal Sirt1. In conclusion, our results suggest that resveratrol attenuates the hippocampus-dependent cognitive impairment induced by isoflurane anesthesia through its anti-inflammation and anti-apoptosis effects in aged mice.

Spinal neuroimmune activation inhibited by repeated administration of pioglitazone in rats after L5 spinal nerve transection.

Neuroimmune activation contributes to the generation and maintenance of neuropathic pain after peripheral nerve injury. Peroxisome proliferator activated receptor gamma (PPAR-γ) agonists have potential neuroprotection. The current study aimed to determine the effects of a PPAR-γ agonist pioglitazone on mechanical hyperalgesia and neuroimmune activation in a rat model of neuropathic pain induced by L5 spinal nerve transection (SNT). Thirty-two rats were equally randomized into 4 groups: sham operation with vehicle; L5 SNT with vehicle or pioglitazone; or L5 SNT with pioglitazone and a PPAR-γ antagonist GW9662. Pioglitazone or vehicle was administered 1h before operation and continued daily to day 14 after operation. The paw pressure threshold (PPT) was measured before operation and on days 3, 7, 14 after operation. Glial fibrillary acidic protein (GFAP) expression, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 levels, and nuclear factor-kappa B (NF-κB) activity in the lumbar spinal cord were determined on day 14 after operation. The results displayed pioglitazone improved the mechanical hyperalgesia, and attenuated the astrocyte and NF-κB activation and the inflammatory cytokine upregulation in nerve-injured rats, which might be reversed by GW9662. In conclusion, pioglitazone ameliorates the mechanical hyperalgesia induced by L5 SNT via inhibiting the spinal neuroimmune activation in rats, suggesting spinal PPAR-γ signaling pathway may be involved in the pathogenesis of mechanical hyperalgesia.

Intragenic recombination as a mechanism of genetic diversity in bluetongue virus.

Bluetongue (BT), caused by Bluetongue virus (BTV), is an economically important disease affecting sheep, deer, cattle, and goats. Since 1998, a series of BT outbreaks have spread across much of southern and central Europe. To study why the epidemiology of the virus happens to change, it is important to fully know the mechanisms resulting in its genetic diversity. Gene mutation and segment reassortment have been considered as the key forces driving the evolution of BTV. However, it is still unknown whether intragenic recombination can occur and contribute to the process in the virus. We present here several BTV groups containing mosaic genes to reveal that intragenic recombination can take place between the virus strains and play a potential role in bringing novel BTV lineages.

[Synthesis of the CaCO3:Eu3+ red phosphor by microwave method].

The red phosphor of CaCO3 doped with Eu3+ was synthesized with the microwave method in the aqueous solution and characterized with electron microscope (SEM), X-ray diffraction (XRD), and photoluminescence and photoluminescence excitation (PL-PLE) spectrum. Also under investigation was the influence of microwave power on luminescence properties. The results showed that the synthesized CaCO3:Eu+ particles were the mixture of various particles in the forms of vaterite with flower-flake, calcite with cubic shape and aragonite with needle-like, which were evenly dispersed. The Eu3+ ion as the luminescent center inhabited the site of Ca3+ in mixed phases of CaCO3:Eu3+. This feature was mainly characterized by the intense charge transfer band range from 200 to 300 nm in the PLE spectrum, which was the wide band excitation. Moreover, the narrow excitation peaks at 319, 395, 465, 535 nm and so on could be detected in the PLE spectrum. For the mixed phase, the magnetic-dipole transition (5)D0 to (7)F1 emission was split into two sublevels at about 589 and 593 nm by the crystal field. The mainly emission peaks were located in the vicinity of 614 and 620 nm, corresponding to the electric dipole transition (1)D0-->(7)F2 of Eu3+ ions that was the pure red emission. Moreover, with the improvement of the microwave power, the emission intensity was on rise for the morphology and phase of the sample changed from the flower-flake vaterite to the needle-like aragonite, coupled with the intensity of red light emission.

Appearance of mosaic enterovirus 71 in the 2008 outbreak of China.

Enterovirus 71 (EV71) is a pathogen of hand-foot-and-mouth disease (HFMD). In the last year and this spring, HFMD caused by EV71 repeatedly broke out and has resulted in at least 50 children's death in China. It is important to know the mechanism effecting genetic diversity of the virus circulating in China in order to prevent future outbreaks in the country. Homologous recombination has been proved to play a role in evolution of the virus. In this study, we have performed a phylogenetic analysis of full-length EV71 isolated in the last year in China to detect if recombination exerts its influence on the EV71 outbreak. Among EV71 isolates from China, 5 isolates were identified as mosaic. This finding suggests that homologous recombination has played some roles in generating genetic diversity in the outbreak of EV71 in China.