ABSTRACT
The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.
Subject(s)
Humans , Action Potentials , HEK293 Cells , Protein Kinase C/metabolism , Pyramidal Cells/enzymology , Shab Potassium Channels/geneticsABSTRACT
Objective:To investigate the effects of human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-ex) on proliferation, migration, apoptosis and autophagy in ischemia-anoxia neurons, and to provide a theoretical study for clinical research on stroke.Methods:Primary glial cells were cultured and OGD model was established. Then, these cells were incubated with huMSC-exosome. The inhibition rate of proliferation was detected by MTT assay. Apoptosis was observed by flow cytometry. The expressions of apoptosis related proteins were confirmed by RT-PCR and Western blot. The expressions of autophagy related proteins and PI3K/Akt signal were observed by Western blot. The data were analyzed using SPSS 17.0 software, multiple-group comparisons were performed using one-way ANOVA, and SNK- q test was used for pairwise comparison between groups. Results:MTT assay showed that OGD could inhibit cell proliferation of primary glial cells. After incubation with hucMSC-ex for 2 h, the inhibition rate of cell proliferation was lower than that of the control. The flow cytometry technology showed that hucMSC-ex reduced cell apoptosis. The cell migration experiments showed that OGD reduced cell migration capacity, but cell migration increased after exosomal incubation. RT-PCT and Western blot showed that OGD induced autophagy and apoptosis, hucMSC-ex activated PI3K/Akt signaling pathway, inhibited the expression of Bax and Caspase-3 (both P<0.05), and promoted the expression of Bcl-2 ( P<0.05). hucMSC-ex inhibited the expression of Beclin-1, Atg3 and LC3-Ⅱ(al l P<0.01). Conclusions:huMSC-exosome promote the proliferation and migration in ischemia-anoxia-injured neurons and inhibit the apoptosis and autophagy. The mechanism that hucMSC-ex repaired the injured nerve cells might be associated with PI3K/Akt signaling pathway.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between the maxillary sinus flow field, temperature field and the maxillary sinus ostium size, and to provide a reference for endoscopic surgery according to the maxillary sinus scope.</p><p><b>METHODS</b>One case of adult female CT image data was obtained, and used to build a three-dimensional model of nasal cavity and maxillary sinus. Computational fluid dynamics method was used to study the airflow and temperature of the maxillary sinus, as well as the physiological function of the maxillary sinus. Simulation surgery by means of different maxillary sinus diameters (normal, 8 mm, 10 mm, 12 mm and 15 mm) was used to describe the maxillary sinus airflow and temperature change.</p><p><b>RESULTS</b>It was found that by numerical simulation the airflow of maxillary sinus and nasal cavity showed lower speed (average speed 0.062 m/s) than that in the middle nasal meatus (average speed of 3.260 m/s), and the average temperature in the normal maxillary sinus was 34°C, which was higher than that in the middle nasal meatus (temperature 28.7°C). With the increase of the diameter of the maxillary sinus, the air temperature change was not obvious.</p><p><b>CONCLUSIONS</b>The physiological function of the maxillary sinus can be studied through the numerical simulation. With the increase of the ostia diameter of maxillary sinus, the sinus temperature and ventilation is not affected. It provides a reference for quantification of clinical endoscopic maxillary sinus surgery.</p>
Subject(s)
Adult , Female , Humans , Endoscopy , Hydrodynamics , Maxillary Sinus , Models, Theoretical , Nasal Cavity , Respiration , Temperature , Tomography, X-Ray ComputedABSTRACT
[ABSTRACT]OBJECTIVETo evaluate the curative effect of endoscopic sinus surgery from the viewpoint of biomechanics analysis.METHODSWe select one case undergoing nasal endoscopic surgery for chronic sinusitis patients, after half year follow-up and collect preoperative and postoperative spiral CT data to build a numerical model of nasal cavity and paranasal sinuses with computer numerical simulation (CFD) research methods, to explore nasal airflow distribution and flow field characteristics of value changes before and after the operation. Patients undergo subjective assessments: nasal obstruction of VAS score, olfactory VAS score, SNOT-20, objective assessment: Lund Kennedy score, Lund Mackay score, saccharin test time and acquisition clinical efficacy data to verify the credibility of the analysis method is feasible and the results. RESULTSThe nasal resistance after endoscopic sinus surgery in nasal cavity and paranasal sinuses numerical simulation decreased, middle meatus of nose and nasal air flow velocity decreased, the pressure change slightly;nasal threshold region, middle turbinate head end section in maxillary sinus ostium section, after nearly sieve horizontal cross-section average velocity decreased, nasal airflow for the mucosa of the shear stress reduced. The volume of the nasal cavity and the area of the mucosa was increased, the volume ratio was decreased, the subjective and subjective assessment of the patients was improved, and the objective assessment was lighten.CONCLUSIONAerodynamic rules are presented through the calculation of numerical simulation of fluid mechanics which is invisible before. Better understanding of changes in the nasal airflow distribution and the changes of flow field characteristics can be useful to establish nasal endoscopic surgery in numerical analysis of offshore platform,which provides a new research tool for the understanding of the pathophysiology of chronic sinusitis by endoscopic sinus surgery.
ABSTRACT
[ABSTRACT]OBJECTIVETo compare the differences of aerodynamic characteristics of pharyngeal cavity between normal subjects and OSAHS patients, and to study the nasal obstruction in the pathogenesis of the OSAHS.METHODSA total of 60 normal subjects and 60 OSAHS patients were enrolled in this study. Numerical simulation was performed to calculate the airflow dynamic indexes of three sections of pharyngeal cavity. Correlation analysis of the nasal resistance and negative pressure were studied.RESULTSThe average pharyngeal negative pressure and airflow velocity in OSAHS patients were significantly increased than that in normal subjects. The total nasal airway resistance significantly correlated with the average negative pressure of pharyngeal cavity. CONCLUSIONAirflow dynamic indexes of OSAHS patients had significant different pharyngeal aerodynamic characteristics from normal subjects. The increased average negative pressure in pharynx might contribute to the severity of pharyngeal collapse for OSAHS patients. Higher total nasal resistance might play a role in the pathophysiological mechanisms of OSAHS.