Metabolic modulation of neuronal excitability is becoming increasingly important as an antiepileptic therapy. It was reported that the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) and the activation of the ATP-sensitive potassium ion channel (K(ATP) channel) had an antiepileptic effect in models of epilepsy. To explore whether 2-DG exerts an antiepileptic effect through upregulation of the K(ATP) channel subunits Kir6.1 and Kir6.2, the expression of these subunits in hippocampus of five groups of mice with pilocarpine-induced status epilepticus (SE) was evaluated. A seizure group with pilocarpine-kindling convulsions (EP) was compared to similar groups treated with high, medium, and low 2-DG concentrations (100-500 mg/kg) and a normal control group (Con). Kir6.1 and Kir6.2 mRNAs and proteins were analyzed at 4 h, 1 days (acute period), 7 days (latent period), 30, and 60 days (chronic period) following SE. In the seizure group (compared to the Con group), hippocampal expression of Kir6.1 and Kir6.2 increased dramatically at 1, 7, and 30 days, and was further increased after treatment with medium and high dose 2-DG (all P < 0.05). Our results suggest that 2-DG may exert an antiepileptic effect through up-regulation of mRNAs and protein levels of Kir6.1 and Kir6.2, which may therefore be used as molecular targets in the treatment of epilepsy with 2-DG.

BackgroundThis study aimed to investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on IL-6, TNF-α, and IL-10 secretion in LPS-activated RAW 264.7 cells and human peripheral blood mononuclear cells (PBMCs) in vitro and to explore the related signaling pathways of the regulation mechanisms of BNP in systemic inflammatory response syndrome (SIRS).Material/MethodsMTT assay was used to evaluate the effects of rhBNP on cell viabilities. Lipopolysaccharide (LPS) was used to induce inflammation response. The whole study was divided into 8 groups: Control, low, middle, and high concentrations of rhBNP, LPS, LPS with low, middle, and high concentrations of rhBNP. Levels of IL-6, TNF-α, and IL-10 were evaluated using the Cytometric Bead Array Kit and RT-PCR assay. Western blotting was used to test the effects of rhBNP on inflammation-related NF-κB and MAPK pathways.ResultsExcept for the concentrations ≥1.6 ng/mL, all concentrations of rhBNP showed little effect on cell viabilities of RAW264.7 cells and PBMCs after 24 h and 48 h, suggesting a weak cytotoxicity to cells. Expression of IL-6 and TNF-α significantly increased and expression of IL-10 significantly decreased at protein and mRNA levels after LPS treatment, and these effects were strongly inhibited in a dose-dependent manner by pretreatment of rhBNP. Similarly, the LPS-induced increase of NF-κB and MAPK pathway phosphorylation levels were also significantly inhibited by rhBNP.ConclusionsrhBNP can regulate expression of IL-6, TNF-α, and IL-10 in LPS-activated RAW 264.7 cells and PBMCs through inhibiting NF-κB and MAPK pathways. These results may reveal potential causes of the increase of BNP in SIRS and may provide an experimental basis for treatment of SIRS.

Background Psittacosis pneumonia is a community-acquired pneumonia caused by Chlamydia psittaci. It is usually under-diagnosed due to its atypical clinical presentation and lack of routine laboratory tests. Methods To better understand the clinical features, 52 patients diagnosed with psittacosis pneumonia by metagenomic next-generation sequencing (mNGS) were enrolled in this study. The clinical, radiological and pathological characteristics were retrospectively analyzed. Results The onset of psittacosis pneumonia in this study occurred all year round, with a peak from December to January. Most of the patients were 51–80 years old. About 65.38% of patients had a history of exposure to poultry or parrots. Abnormalities of multiple clinical signals were detected in these patients. Elevated levels of neutrophil ratio, C-reactive protein, erythrocyte sedimentation rate, and procalcitonin were detected in most patients. Radiological evidence revealed air-space consolidation or ground-glass opacities in lungs of all patients, which is the typical feature of psittacosis pneumonia. In addition, hyperemia, swelling of bronchial mucosa, and bronchial patency were detected by bronchoscopy in all patients, and bronchial sub-mucosal edema, inflammatory cells infiltration and alveolar epithelial hyperplasia were identified in the bronchial mucosa and alveolar tissue. Beta-lactam antibiotics were administered for empirical treatment before mNGS in 17 patients but showed no improvement. The treatment was switched to doxycycline or moxifloxacin immediately since psittacosis pneumonia were suspected and confirmed by mNGS detection (within 48 hours). After receiving adjustment of treatment, 94.23% (49/52) of patients were cured successfully. Conclusions In conclusion, mNGS may be a promising approach for clinical diagnosis of psittacosis. For patients with a history of exposure to birds, hyperpyrexia, nonproductive cough, multiple elevated inflammatory markers, and air-space consolidation in lung, psittacosis pneumonia should be considered, especially when beta-lactam antibiotics showed limited efficacy.