Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels

ATP-sensitive potassium channels (K) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic K channels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore important drug targets. Here, we present three structures of pancreatic K channels solved by cryo-electron microscopy (cryo-EM), at resolutions ranging from 4.1 to 4.5 Å. These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6.2 (inward-rectifying potassium channel 6.2) N-terminus participates in the coupling between the peripheral SUR1 (sulfonylurea receptor 1) subunit and the central Kir6.2 channel, reveal the binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP binding on nucleotide binding domains (NBDs) drives a conformational change of the SUR1 subunit.

Clinical characteristics and treatment assessments of severe enterovirus 71 infected children / 中华儿科杂志

<p><b>OBJECTIVE</b>To facilitate early recognition of ominous clinical manifestations, to understand pathophysiology and assess treatment effects in patients with severe enterovirus 71 (EV71) associated hand, foot and mouth disease (HFMD).</p><p><b>METHOD</b>A retrospective analysis was performed based on the clinical records, laboratory data and treatment effects which were collected from twelve severe EV71 infected cases from nine hospitals in 2008, in Hubei province, China.</p><p><b>RESULT</b>Of the 12 severe cases, ten (83.3%) were male and two female. The median age was 1.96 yrs (8 m to 7 yrs). The mean hyperthermic duration was 6 days with the peak temperature over 38.5 degrees C, and mean rash duration was 7 days. Fever and rash emerged simultaneously in 4 of 5 cases with cardiopulmonary failure. The severe complications included encephalitis (10 cases), pulmonary edema or hemorrhage (5 cases). Eleven cases were checked with magnetic resonance imaging (MRI) and four cases showed characteristics of encephalitis or meningitis, two with images of naso sinusitis and ethmoid-mastoid inflammation. Chest X-ray examination showed with pulmonary edema on single or both sides (5 cases), bronchitis (4 cases), and normal image (3 cases). There was no specific finding in the cardiac ultrasound and electrocardiogram in any of the patients, as well as the white blood cell count, blood glucose, prothrombin time, partial thromboplastin time and D-dimer. Cerebrospinal fluid showed aseptic meningitis with the increase of cell count in 7 cases. All patients were treated with antibiotics and/or antivirals, such as cephalosporins, ribavirin etc. Eleven patients were treated with intravenous immunoglobulin (total dose 2 - 4.5 g/kg) for 2 - 5 days, and the highest blood concentration of immunoglobulin was detected increasing at 7 g/L. Seven cases were also treated with methylprednisolone 10 - 30 mg/(kg x d), four with dopamine, dobutamine, or digitalis. In addition, by using continuous positive airway pressure by nasal catheter and maintenance of circulation in the cases with cardiopulmonary failure could not relieve the symptoms of dyspnoea, and mechanical ventilation was required to maintain for a mean of 72 hrs (24 - 96 hrs). Except one case died of pulmonary edema in the early stage, others were cured without sequelae.</p><p><b>CONCLUSION</b>Severe EV71 infection is more common in children younger than 3 years old, in which the profound complications include encephalitis and pulmonary edema. The mechanical ventilation should be critically urged for child with complicating cardiopulmonary failure as soon.</p>

Effects of supernatant of cord blood CD3AK cells on proliferation, differentiation and apoptosis of HL-60 cells / 中华儿科杂志

<p><b>OBJECTIVE</b>The study was to investigate the impact of cord blood CD(3)AK cell culture supernatant (CS) on proliferation, differentiation and apoptosis of HL-60 cells.</p><p><b>METHODS</b>HL-60 cells were treated with different concentrations of CS (10%, 15%, 20%) for 3 days, 6 days and 9 days, and the same cells of control group were not treated with CS. The growth of induced cells was assessed with Trypan blue staining and cell counting with cytometer. The differentiation marker CD(11b) on the cell surface and cell-cycle was analyzed by flow cytometry (FCM), cell morphology (Wright-Giemsa staining) and NBT test to determine the extent of differentiation. Meanwhile, the changes of the apoptosis of the cells induced by 20% CS at different time points (3, 6 and 9 days) were analyzed by TUNNEL-POD, and the apoptotic characteristics of cells were observed.</p><p><b>RESULTS</b>The growth of HL-60 cell was inhibited as CS-inducing time and the dose of CS increased. At the same time, but HL-60 cell number in G(0)/G(1) phase of cell-cycle increased, but HL-60 cell number in S phase decreased compared with untreated group. The HL-60 cells induced by 20% CS for 9 days showed that (52.7 +/- 1.8)% of cells were at G(0)+G(1) phase and (43.8 +/- 1.1)% were at S phase (P < 0.05), which demonstrated that HL-60 cells induced by 20% CS underwent G(0)/G(1) phase cell-cycle arrest. The volume of the differentiated cells was enlarged gradually as CS-inducing time prolonged. After 3 days the differentiating cells began to express differentiating marker CD(11b) on the cell surface and the nuclei morphology of the differentiated cells was also changed and NBT-stained cells increased in number with the increased dose of CS increased. Three days after induction by 20% CS, the induced cells began to show signs of apoptosis and the apoptotic percentage of induced cells gradually increased with CS-induction time. The rate of apoptosis of cells was (33.3 +/- 2.3)% at 9 days (P < 0.01).</p><p><b>CONCLUSION</b>CS could not only inhibit the growth of HL-60 cells but also induce the differentiation and apoptosis in HL-60 cells.</p>

Survivin expression in midline T-cell lymphoma in relation to Epstin-Barr virus infection / 中国实验血液学杂志

To investigate the expression of survivin gene and its relationship with Epstin-Barr virus (EBV) infection in midline T-cell lymphoma (MTL), immunohistochemistry staining method was used to examine the expression of survivin and EBV-latent membrane protein (LMP-1) in the 41 cases. In situ hybridization (ISH) was used to detect EBV-encoded RNA (EBER1/2). The results showed that the expression of survivin was positive in 26 cases of midline T-cell lymphoma, but no positive was detected in 10 cases of reactive lymphoid tissues. The positive expression ratio of survivin was 12.5% in cases of MTL with low grade of malignancy, and was 75.76% in cases of MTL with middle and high grades of malignancy, the significant difference was found between these two groups (chi(2) = 8.55, P < 0.01). Positive expression ratios of EBER1/2 and LMP-1 were 70.73% and 41.46% respectively. Survivin expression was not significantly different between EBER1/2 positive and negative cases (P > 0.05). It is concluded that survivin expression is up-regulated in MTL, and survivin positive expression rate is associated with the degree of malignancy. Survivin may play a role in the pathogenesis of the MTL by influencing cell apoptosis. EBV infection is not significantly associated with survivin expression in the MTL.

Correlation between Mitochondrial Membrane Potential and Topiramate′s Neuroprotection / 实用儿科临床杂志

Objective To study topiramate′s neuroprotection on primary cultured hippocampal neurons which were injuried by glutamate and its mechanism.Methods The primary cultured hippocampal neurons were made as the research object,and excitotoxicity model was exected with glutamate.Hippocampal neuron survival was assessed by MTT method and hippocampal neuron mitochondrial membrance potential(MMP) was evaluated by fluorescence microscope and flow cytometry.Results Hippocampal neuron survival of normal control was(98.4?0.8)%,and the survival of glutamate model group was(59.6?3.2)%,at the same time,two topiramate′s groups′ cell survivals was(74.1?0.5)% and(79.2?3.4)%,and topiramate with two levels all could obviously increase hippocampal neuron survival((P

Significance of Detection of Chemokines in Serum of Infants Respiratory Syncytial Virus Infection / 实用儿科临床杂志

Objective To explore the roles of macrophage inflammatory protein- 1?(MIP- 1?) and regulated upon activation normal I" cell expressed and secreted(RANTES)in pathogenesis of respiratory syncytiai virus(RSV) infection,and explore the roles of these chemokines asthma caused by RSV mfectron. Methods Serum samples were obtained from 45 infants with RSV infection, including 10 hroivhial asthma, 15 bronchitis or pneumonia ,20 upper respiratory tract infection ;20 healthy infants with non - RSV infection as the normal group. ELISA method was used to determine the concentrations of MIP- 1? and RANTES in serum. Results MIP - 1? and RANTES levels in infants with RSV infection were much higher than those of non - RSV infected healthy subjects (P

Immunophenotypic Features of NK/T Cell Lymphoma in Children and Its Association with Epstein-Barr Virus / 实用儿科临床杂志

Objective To study the immunophenotypic features of NK/T cell lymphoma in children and its association with Epstein-Barr virus (EBV) infection. Methods Five cases of children′s NK/T cell lymphoma were studied. CD45RO, CD3?, CD56, CD20, TIA-1 and granzyme B were detected by immunohistochemistry staining for investigating immunophenotype. The expression of EBV-latent membrane protein (LMP-1) were detected by immunohistochemistry. EBV-encoded RNA (EBER1/2) were detected by in situ hybridization (ISH). Results CD45RO, CD3?, TIA-1 and granzyme B were positive in 5 cases, CD56 was positive in 2 cases, while CD20 negative in 5 cases.EBER1/2 positive in 4 cases and LMP-1 positive in 3 cases.Conclusions NK/T cell lymphoma in children is strong associated with EBV infection,and EBV infection may play an important role in the pathogenesis of children NK/T cell lymphoma.