Perifosine inhibits biofilm formation of Pseudomonas aeruginosa by interacting with PqsE protein / 中华预防医学杂志

To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 μg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.

Pathological changes in the epileptogenic foci of children with intractable epilepsy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate pathological changes in the epileptogenic foci of children with intractable epilepsy and their clinical significance.</p><p><b>METHODS</b>Thirty children with intractable epilepsy were included in the study. The epileptogenic foci were surgically resected and pathological changes in the obtained specimens were observed under a light microscope (LM) and a transmission electron microscope (TEM).</p><p><b>RESULTS</b>Under the LM, cortical dysplasia was found in 14 cases (47%), hippocampal sclerosis in 11 cases (37%), dysembryoplastic neuroepithelial tumor in 1 case (3%), ganglioglioma in 1 case (3%), and encephalomalacia in 3 cases (10%). The TEM observation revealed pathological changes in the ultrastructure of the hippocampus and extra-hippocampal cortex, such as changes in the number of synapses and synaptic structure, decrease in neurons and karyopyknosis, swelling and degeneration of astrocytes, and changes in mitochondrial structures.</p><p><b>CONCLUSIONS</b>Pathological changes in the hippocampus and extra-hippocampal cortex, especially synaptic remodeling, may be the morphological basis for spontaneous recurrent seizures in children with intractable epilepsy. The pathological changes and epileptiform activity are related to an imbalance between excitatory and inhibitory neurotransmission.</p>