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Kui Chen - Top 30 Publications

Evaluation of PDQ-8 and its relationship with PDQ-39 in China: a three-year longitudinal study.

Parkinson's disease is characterized by motor and non-motor symptoms with wide ranging impacts on the health-related quality of life. The 39-item Parkinson's disease Questionnaire (PDQ-39) is the most widely used PD-specific health-related quality-of-life questionnaire. The short-form 8-item Parkinson's disease Questionnaire (PDQ-8) was found to produce results similar to that of the PDQ-39 cross-culturally. However, there is no evaluation of the PDQ-8 in the mainland of China.

A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome.

Perrault syndrome is a rare multisystem disorder that manifests with sensorineural hearing loss in both sexes, primary ovarian insufficiency in females and neurological features. The syndrome is heterogeneous both genetically and phenotypically.

Fullerenol nanoparticles suppress RANKL-induced osteoclastogenesis by inhibiting differentiation and maturation.

Bone health requires regulation of homeostatic equilibrium between osteoblasts and osteoclasts. The over-activation of osteoclasts can disrupt bone metabolism, resulting in osteoporosis and other bone-loss diseases. Fullerenol, a polyhydroxy derivative of fullerene, exhibits excellent biocompatibility. Here we show that fullerenol nanoparticles exert two functions: inhibition of osteoclastic differentiation and blockage of pre-osteoclast fusion to restructure osteoclast maturation and function. Experimentally, the nanoparticles reduced pre-osteoclast migration and inhibited ruffled border formation to block their maturation. In addition, fullerenol dose-dependently restricted the differentiation of bone marrow macrophage cells (BMMs) to form osteoclasts following treatment with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB (RANKL) to activate NF-κB and mitogen activating protein kinase (MAPK) signaling pathways. It is possible that the very small size of fullerenol allows it to directly cross the cellular membrane to access the cytoplasm and regulate osteoclastogenesis from BMMs. Our results suggest that fullerenol could be used to treat bone-loss diseases such as osteoporosis.

Propofol attenuates intermittent hypoxia induced up-regulation of proinflammatory cytokines in microglia through inhibiting the activation of NF-Bκ/p38 MAPK signalling.

<i>As immune sentinels of the central nervous system (CNS), microglia is pivotal cellular mediator of neuroinflammatory processes. Activation of microglia might elicit the expression of proinflammatory cytokines involved in the progression of neuroinflammatory diseases. Numerous studies have demonstrated that propofol (2,6-diisopropylphenol) has an effective anti-inflammatory property. Intermittent hypoxia (IH), as a result of obstructive sleep apnoea (OSA), could lead to neuron damage and neuroinflammation in the CNS. Here, we determined the effects of propofol on the inflammatory response in microglia during IH. The levels of nuclear factor-Bκ (NF-κB) inhibitor (IκB) and activated p38 mitogen-activated protein kinase (MAPK) exposed to IH with or without propofol treatment were detected by Western blot. The viability of cells exposed to various concentrations of propofol was monitored with MTT assay. The production and mRNA levels of tumor necrosis factor- α(TNF-α) and interleukin-6 (IL-6) were evaluated by qRT-PCR and ELISA, respectively. As results, IH exposure obviously promoted the activation of NF-κB/p38 MAPK signalling and the secretion of TNF-α and IL-6. Propofol was not toxic to microglia. Compared with the control group, propofol attenuated the IH-induced activation of NF-Bκ and p38 MAPK, which accompanied with reduction of proinflammatory cytokine secretion. These data suggested that propofol down-regulated the IH-induced secretion of proinflammatory cytokine, and inhibit inflammatory responses in microglia, and might be involved in attenuation of the p38 MAPK and NF-κB signalling pathways. Overall, propofol could contribute to alleviating IH-induced CNS diseases in patients by inhibiting p38 MAPK and NF-κB mediated inflammation in microglia.</i>.

Olfaction in Parkin carriers in Chinese patients with Parkinson disease.

Olfactory identification was reported to be better among PD (Parkinson disease) patients with Parkin mutations, but previous studies didn't eliminate the interference of other PD related genes on olfaction, and whether olfaction of Parkin mutations patients was better in Chinese population was still unknown.

Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice.

Excessive consumption of diets high in sugars and saturated fat, frequently known as western diet (WD), may lead to obesity and metabolic syndrome. Recent evidence shows that WD-induced obesity impairs cardiac function, but the underlying mechanisms are not fully understood. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. We tested the hypothesis that elevated circulating TMAO levels contribute to cardiac dysfunction in WD-induced obesity. CD1 mice were fed a normal diet (ND) or a WD, without or with 1.0% 3,3-Dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) in drinking water for 8 weeks. Compared with mice fed a ND, mice fed a WD showed a significant increase in body weight and dyslipidemia, and had markedly higher plasma TMAO levels at the end of the feeding protocol. Echocardiography revealed that cardiac systolic and diastolic function was impaired in mice fed a WD. DMB treatment had no effects on body weight and dyslipidemia, but significantly reduced plasma TMAO levels and prevented cardiac dysfunction in mice fed a WD. In addition, mice fed a WD had elevated expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin IL-1β, decreased expression of anti-inflammatory cytokine IL-10, and increased interstitial fibrosis in the hearts, all of which were prevented by DMB treatment. Notably, DMB treatment also reduced plasma TMAO levels in mice fed a ND but did not alter other parameters. These results suggest that consumption of a WD increases circulating TMAO levels, which lead to cardiac inflammation and fibrosis, contributing to cardiac dysfunction. Interventions that reduce circulating TMAO levels may be a novel therapeutic strategy for prevention and treatment of WD-induced cardiac dysfunction.

Correction to Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.

pH of Aerosols in a Polluted Atmosphere: Source Contributions to Highly Acidic Aerosol.

Acidity (pH) plays a key role in the physical and chemical behavior of PM2.5. However, understanding of how specific PM sources impact aerosol pH is rarely considered. Performing source apportionment of PM2.5 allows a unique link of sources pH of aerosol from the polluted city. Hourly water-soluble (WS) ions of PM2.5 were measured online from December 25th, 2014 to June 19th, 2015 in a northern city in China. Five sources were resolved including secondary nitrate (41%), secondary sulfate (26%), coal combustion (14%), mineral dust (11%), and vehicle exhaust (9%). The influence of source contributions to pH was estimated by ISORROPIA-II. The lowest aerosol pH levels were found at low WS-ion levels and then increased with increasing total ion levels, until high ion levels occur, at which point the aerosol becomes more acidic as both sulfate and nitrate increase. Ammonium levels increased nearly linearly with sulfate and nitrate until approximately 20 μg m(-3), supporting that the ammonium in the aerosol was more limited by thermodynamics than source limitations, and aerosol pH responded more to the contributions of sources such as dust than levels of sulfate. Commonly used pH indicator ratios were not indicative of the pH estimated using the thermodynamic model.

Efficacy, acceptability and tolerability of 8 atypical antipsychotics in Chinese patients with acute schizophrenia: A network meta-analysis.

We aimed to create hierarchies of the efficacy, acceptability and tolerability of eight atypical antipsychotics in the treatment of Chinese patients with acute schizophrenia.

Inhibition of long non-coding RNA IGF2AS protects apoptosis and neuronal loss in anesthetic-damaged mouse neural stem cell derived neurons.

In vitro culture of neural stem cell-derived neurons serves as an excellent model to study anesthetic-induced neurotoxicity. In our study, we examined the functional role of long non-coding RNA, IGF2AS, in regulating ketamine-induced neurotoxicity in murine neural stem cells.

Endocytosed nanoparticles hold endosomes and stimulate binucleated cells formation.

Nanotechnology developed rapidly in cellular diagnosis and treatment, the endocytic system was an important pathway for targeting cell. In the research of developing macrophages as drug carriers or important therapeutic targets, an interesting phenomenon, internalized nanoparticles induced to form binucleated macrophages, was found although the particles dose did not cause obvious cytotoxicity.

Observation of aerosol number size distribution and new particle formation at a mountainous site in Southeast China.

To quantify the physical/chemical properties, and the formation and growth processes of aerosol particles on mountainous regions in Southeast China, an intensive field campaign was conducted from April to July 2008 on the top of Mt. Huang (1840m above mean sea level). The average particle number concentration was 2.35×10(3)cm(-3), and the ultrafine particles (<0.1μm) represented 70.5% of the total particle number concentration. Excluding the accumulation mode particles, the average daytime particle number concentrations were prominently higher than those measured at nighttime, suggesting there was a diurnal pattern of changes between planetary boundary layer and free troposphere air. The aerosol spectra were classified into two categories: the first category (FCS) exhibited a clear diurnal cycle, with relatively higher number concentration (3.19×10(3)cm(-3)), smaller sizes and air masses from the inland; the second category (SCS) presented less obvious diurnal cycle, with lower number concentration (1.88×10(3)cm(-3)), larger sizes and air masses from coastal regions. Air mass sources, weather conditions, and new particle formation (NPF) events were responsible for the differences of these two particle spectra. Six NPF events were identified, which usually began at 10:00-11:00 LT, with the estimated formation rate J10 in the range of 0.09-0.30cm(-3)s(-1) and the growth rate at 1.42-4.53nmh(-1). Wind speed, sulfur dioxide and ozone concentrations were higher on NPF days than those on non-NPF days, whereas temperature, relative humidity, concentrations of nitrogen oxide and carbonic oxide were lower on NPF days. Sulfur dioxide and ozone might be main potentially precursor gases for those NPF events. The NPF events at Mt. Huang corresponded closely to a southwest winds. These results are useful for improving our understanding of the main factors controlling the variation of aerosol size distribution and NPF events in this region.

Odor Identification Test in Idiopathic REM-Behavior Disorder and Parkinson's Disease in China.

Olfactory dysfunction is common in Parkinson's disease (PD) and idiopathic rapid eye movement sleep behavior disorder (iRBD), which is a risk factor in the development of PD. However, a few studies have conflicting results when comparing dysosmia in the patients with iRBD and PD. There is no study investigating the olfactory function in Chinese patients with iRBD. Additionally, the Sniffin' Sticks screening 12 test (SS-12) contains several odors that are not familiar to people in different cultures.

Inhibition of long non-coding RNA IGF2AS has profound effect on inducing neuronal growth and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion neurons.

Long non-coding RNA IGF2AS was initially identified as a cancer regulator in wilm's tumors. In this study, IGF2AS was investigated of its functions in inducing neural development and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion (DRG) in spinal cord.

Intermittent hypoxia reduces microglia proliferation and induces DNA damage in vitro.

Intermittent hypoxia (IH), caused by obstructive sleep apnea (OSA), could cause hippocampus or neuron damage through multiple signaling pathways, while the underlying mechanisms are still unclear. Thus, the present study aimed to explore the effect of IH on the biological functions of microglia cells.

Utilizing Gold Nanoparticle Probes to Visually Detect DNA Methylation.

The surface plasmon resonance (SPR) effect endows gold nanoparticles (GNPs) with the ability to visualize biomolecules. In the present study, we designed and constructed a GNP probe to allow the semi-quantitative analysis of methylated tumor suppressor genes in cultured cells. To construct the probe, the GNP surfaces were coated with single-stranded DNA (ssDNA) by forming Au-S bonds. The ssDNA contains a thiolated 5'-end, a regulatory domain of 12 adenine nucleotides, and a functional domain with absolute pairing with methylated p16 sequence (Met-p16). The probe, paired with Met-p16, clearly changed the color of aggregating GNPs probe in 5 mol/L NaCl solution. Utilizing the probe, p16 gene methylation in HCT116 cells was semi-quantified. Further, the methylation of E-cadherin, p15, and p16 gene in Caco2, HepG2, and HCT116 cell lines were detected by the corresponding probes, constructed with three domains. This simple and cost-effective method was useful for the diagnosis of DNA methylation-related diseases.

Fullerenol Nanoparticles with Structural Activity Induce Variable Intracellular Actin Filament Morphologies.

Fullerenol nanoparticles are promising for various biological applications; many studies have shown that they induce variable and diverse biological effects including side effects. Separation and purification of two fractions of fullerenols has demonstrated that they have varied chemical structures on the surfaces of their carbon cages. Actin is an important structural protein that is able to transform functional structures under varied physiological conditions. We assessed the abilities of the two fractions of fullerenols to attach to actin and induce variable morphological features in actin filament structures. Specifically the fullerenol fraction with a surface electric charge of -1.913 ± 0.008q (x10(-6) C) has percentages of C-OH and C=O on the carbon cage of 16.14 ± 0.60 and 17.55 ± 0.69. These features allow it to form intermolecular hydrogen bonds with actin at a stoichiometric ratio of four fullerenols per actin subunit. Molecular simulations revealed these specific binding sites and binding modes in atomic details in the interaction between the active fullerenol and actin filament. Conversely, these interactions were not possible for the other fraction of fullerenol with that percentages of C-OH and C=O on the carbon cage were 15.59 ± 0.01 and 1.94 ± 0.11. Neither sample induced appreciable cytotoxicity or acute cell death. After entering cells, active fullerenol binding to actin induces variable morphological features and may transform ATP-actin to ADP-actin. These changes facilitate the binding of ADF/cofilin, allowing cofilin to sever actin filaments to form cofilin/actin/fullerenol rods. Our findings suggest that fullerenol with structural activity binding disturbs actin filament structure, which may inhibit locomotion of cell or induce chronic side effects in to cells.

Porf-2 Inhibits Neural Stem Cell Proliferation Through Wnt/β-Catenin Pathway by Its GAP Domain.

Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the development of brain, the plasticity of the brain network, and the repair for brain function in CNS diseases. The mechanisms regulating NSC behavior are not well elucidated. Previous studies showed porf-2 functions as a modulator in central nerve system development. We here show that porf-2, a conserved family of RhoGAPs, is highly and specifically expressed in NSCs. We also demonstrate that porf-2 inhibits the proliferation of NSCs in vivo and in vitro, but has no effect on NSC differentiation. We investigated which domain is required for the role of porf-2 on NSC proliferation. By using neurosphere formation and Edu assay we confirmed the GAP domain is necessary for its function. In addition, we surveyed a few classical pathways on NSC proliferation and found that porf-2 inhibits NSC proliferation by suppressing the β-catenin nuclear translocation. Taken together, we show for the first time that porf-2 inhibits NSC proliferation through Wnt/β-catenin pathway by its GAP domain.

Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.

Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.

Metabolizer in vivo of fullerenes and metallofullerenes by positron emission tomography.

Fullerenes (C60) and metallofullerenes ([email protected]) have similar chemical structure, but the bio-effects of both fullerene-based materials are distinct in vivo. Tracking organic carbon-based materials such as C60 and [email protected] is difficult in vivo due to the high content of carbon element in the living tissues themselves. In this study, the biodistribution and metabolism of fullerenes (C60 and [email protected]) radiolabeled with (64)Cu were observed by positron emission tomography (PET). (64)Cu-C60 and (64)[email protected] were prepared using 1, 4, 7, 10-tetrakis (carbamoylmethyl)-1, 4, 7, 10-tetra-azacyclodo-decanes grafted on carbon cages as a chelator for (64)Cu, and were obtained rapidly with high radiochemical yield (≥90%). The new radio-conjugates were evaluated in vivo in the normal mouse model and tissue distribution by small animal PET/CT imaging and histology was carried out. The PET imaging, the biodistribution and the excretion of C60 and [email protected] indicated that C60 samples have higher blood retention and lower renal clearance than the [email protected] samples in vivo and suggested that the differences in metabolism and distribution in vivo were caused by the structural differences of the groups on the fullerene cages though there is chemical similarity between C60 and [email protected]

A closure study of aerosol optical properties at a regional background mountainous site in Eastern China.

There is a large uncertainty in evaluating the radiative forcing from aerosol-radiation and aerosol-cloud interactions due to the limited knowledge on aerosol properties. In-situ measurements of aerosol physical and chemical properties were carried out in 2012 at Mt. Huang (the Yellow Mountain), a continental background mountainous site in eastern China. An aerosol optical closure study was performed to verify the model outputs by using the measured aerosol optical properties, in which a spherical Mie model with assumptions of external and core-shell mixtures on the basis of a two-component optical aerosol model and high size-segregated element carbon (EC) ratio was applied. Although the spherical Mie model would underestimate the real scattering with increasing particle diameters, excellent agreement between the calculated and measured values was achieved with correlation coefficients above 0.98. Sensitivity experiments showed that the EC ratio had a negligible effect on the calculated scattering coefficient, but largely influenced the calculated absorption coefficient. The high size-segregated EC ratio averaged over the study period in the closure was enough to reconstruct the aerosol absorption coefficient in the Mie model, indicating EC size resolution was more important than time resolution in retrieving the absorption coefficient in the model. The uncertainties of calculated scattering and absorption coefficients due to the uncertainties of measurements and model assumptions yielded by a Monte Carlo simulation were ±6% and ±14% for external mixture and ±9% and ±31% for core-shell mixture, respectively. This study provided an insight into the inherent relationship between aerosol optical properties and physicochemical characteristics in eastern China, which could supplement the database of aerosol optical properties for background sites in eastern China and provide a method for regions with similar climate.

Identification of Human Islet Amyloid Polypeptide as a BACE2 Substrate.

Pancreatic amyloid formation by islet amyloid polypeptide (IAPP) is a hallmark pathological feature of type 2 diabetes. IAPP is stored in the secretory granules of pancreatic beta-cells and co-secreted with insulin to maintain glucose homeostasis. IAPP is innocuous under homeostatic conditions but imbalances in production or processing of IAPP may result in homodimer formation leading to the rapid production of cytotoxic oligomers and amyloid fibrils. The consequence is beta-cell dysfunction and the accumulation of proteinaceous plaques in and around pancreatic islets. Beta-site APP-cleaving enzyme 2, BACE2, is an aspartyl protease commonly associated with BACE1, a related homolog responsible for amyloid processing in the brain and strongly implicated in Alzheimer's disease. Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. The result of proteolysis is modulation of human IAPP fibrillation and human IAPP protein degradation. These results suggest a potential therapeutic role for BACE2 in type 2 diabetes-associated hyperamylinaemia.

Dexmedetomidine-midazolam versus Sufentanil-midazolam for Awake Fiberoptic Nasotracheal Intubation: A Randomized Double-blind Study.

Awake fiberoptic intubation (AFOI) is usually performed in the management of the predicted difficult airway. The aim of this study was to evaluate the feasibility of dexmedetomidine with midazolam (DM) and sufentanil with midazolam (SM) for sedation for awake fiberoptic nasotracheal intubation.

SENP1 inhibits the IH-induced apoptosis and nitric oxide production in BV2 microglial cells.

To reveal SUMOylation and the roles of Sentrin-specific proteases (SENP)s in microglial cells under Intermittent hypoxia (IH) condition would provide more intensive view of understanding the mechanisms of IH-induced central nervous system (CNS) damage. Hence, in the present study, we detected the expression levels of SENPs in microglial cells under IH and normoxia conditions via RT-PCR assay. We found that SENP1 was significantly down-regulated in cells exposure to IH. Subsequently, the effect of IH for the activation of microglia and the potential roles of SENP1 in the SENP1-overexpressing cell lines were investigated via Western blotting, RT-PCR and Griess assay. The present study demonstrated the apoptosis-inducing and activating role of IH on microglia. In addition, we revealed that the effect of IH on BV-2 including apoptosis, nitric oxide synthase (iNOS) expression and nitric oxide (NO) induction can be attenuated by SENP1 overexpression. The results of the present study are of both theoretical and therapeutic significance to explore the potential roles of SENP1 under IH condition and elucidated the mechanisms underlying microglial survival and activation.

Characteristics and mechanisms of extremity injuries caused by mine blasts in shoals.

The characteristics of explosion in water are different from those in air and vary in different water depths. It is important to investigate the characteristics and mechanisms of extremity injuries caused by mine blasts in shoals.

Synthesis of Hemoglobin Conjugated Polymeric Micelle: A ZnPc Carrier with Oxygen Self-Compensating Ability for Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising singlet oxygen ((1)O2) mediated clinical treatment for many tumors. As the source of (1)O2, oxygen plays an important role in the curative effect of PDT. However, the facts of photochemical depletion of oxygen and the intrinsic hypoxic microenvironment of tumors remain the major challenges. In this work, a novel photosensitizer carrier with oxygen self-compensating ability was designed for PDT. It was synthesized via chemical conjugation of hemoglobin (Hb) to polymeric micelles formed by triblock copolymers of poly(ethylene glycol)-block-poly(acrylic acid)-block-polystyrene (PEG-b-PAA-b-PS). The PEG-b-PAA-b-PS and resultant micelles in aqueous solution were comprehensively characterized by means of FTIR, (1)H NMR, GPC, DLS, TEM, and fluorescence spectroscopy. The oxygen-binding capacity and antioxidative activity of the Hb conjugated micelles were evaluated via UV-vis spectroscopy. In addition, compared with the control micelles without Hb, the Hb conjugated photosensitizer carrier was able to generate more (1)O2 and exert greater photocytotoxicity on Hela cells in vitro.

Suppression of miR-221 inhibits glioma cells proliferation and invasion via targeting SEMA3B.

Gliomas are the most common primary tumors in the central nervous system. Due to complicated signaling pathways involved in glioma progression, effective targets for treatment and biomarkers for prognosis prediction are still scant.

Effects of diethylstilbestrol on the proliferation and tyrosinase activity of cultured human melanocytes.

The aim of the present study was to observe the effects of different exogenous estrogen diethylstilbestrol (DES) concentrations on the human melanocyte proliferation and tyrosinase activity. Skin specimens were obtained following blepharoplasty, and the melanocytes were primary cultured and passaged to the third generation. The melanocytes were seeded in 96-well plates, each well had 5×10(3) cells. The medium was changed after 24 h, and contained 10(-4)-10(-8) M DES. After the melanocytes were incubated, the proliferation and tyrosinase activity were detected by the MTT assay and L-DOPA reaction. DES (10(-8)-10(-6) M) enhanced the proliferation of cultured melanocytes. The intensity was positively correlated with the concentration of drug. DES, >10(-5) M, inhibited the melanocytes proliferation or even produced the toxicity effect. Following the addition of 10(-6) M DES to the medium, the tyrosinase activity of melanocytes was significantly increased, with P<0.05. In conclusion, a certain concentration of DES promoted the proliferation of melanocytes, enhanced the activity of tyrosinase and promoted pigment synthesis of melanocytes, with the optimal concentration of 10(-6) M.

Curcumin Protects Neurons from Glutamate-Induced Excitotoxicity by Membrane Anchored AKAP79-PKA Interaction Network.

Now stimulation of AMPA receptor as well as its downstream pathways is considered as potential central mediators in antidepressant mechanisms. As a signal integrator which binds to AMPA receptor, A-kinase anchoring protein 79-(AKAP79-) PKA complex is regarded as a potential drug target to exert neuroprotective effects. A well-tolerated and multitarget drug curcumin has been confirmed to exert antidepressant-like effects. To explore whether AKAP79-PKA complex is involved in curcumin-mediated antiexcitotoxicity, we detected calcium signaling, subcellular location of AKAP79-PKA complex, phosphorylation of glutamate receptor, and ERK and AKT cascades. In this study, we found that curcumin protected neurons from glutamate insult by reducing Ca(2+) influx and blocking the translocation of AKAP79 from cytomembrane to cytoplasm. In parallel, curcumin enhanced the phosphorylation of AMPA receptor and its downstream pathways in PKA-dependent manner. If we pretreated cells with PKA anchoring inhibitor Ht31 to disassociate PKA from AKAP79, no neuroprotective effects were observed. In conclusion, our results show that AKAP79-anchored PKA facilitated the signal relay from AMPA receptor to AKT and ERK cascades, which may be crucial for curcumin-mediated antiexcitotoxicity.

Neuroprotective effects of intravenous lidocaine on early postoperative cognitive dysfunction in elderly patients following spine surgery.

This study aimed to evaluate the effects of lidocaine treatment on cognitive impairment in aged patients undergoing spine surgery and to explore the underlying mechanism.