Effects of H102 on the memory recognition ability and AMPK-mTOR autophagy-related pathway in AD mice / 中国应用生理学杂志

OBJECTIVE@#To study the effect of β-sheet blocking peptide H102 on the expression of AMPK-mTOR autophagy pathway-related protein in APP/PS1 double transgenic AD mice.@*METHODS@#Thirty male APP/PS1 transgenic male AD mice of 6 months old were randomly divided into AD group and H102 intervention group, and C57BL/6J male mice of the same age were used as control group (n=15). The mice in the HF group were administered with 5 μl (5.8 mg/kg) of H102 polypeptide solution through the nasal cavity at the same time period, and the mice in the control group and the AD group were given the same amount of blank adjuvant solution daily. The memory recognition ability was tested by a new object recognition experiment 30 days after continuous administration. Immunohistochemistry and Western blot were used to detect the expressions of phosphorylated AMP-activated protein kinase(P-AMPK),phosphorylated mammalian target of rapamycin (P-mTOR) and ratio of LC32to LC31(LC3II/I )in brain tissue.@*RESULTS@#Compared with the control group, the new object recognition index (RI) of the AD group was significantly lower (P＜0.05), and the P-AMPK and LC3II/I ratios in the brain of the mice were significantly lower (P＜0.05). The expression of P-mTOR protein was increased significantly (P＜0.05). Compared with the AD group, the RI of the H102 intervention group was increased significantly (P＜0.05), and the P-AMPK and LC3II/I ratios in the brain tissue of the mice were increased significantly (P＜0.05). The expression of P-mTOR protein was decreased significantly (P＜0.05).@*CONCLUSION@#H102 can improve the recognition and memory ability of AD mice by activating the AMPK-mTOR autophagy-related pathway.

Single Nucleotide Polymorphism of Mitochondrial DNA D-LOOP Region in Peripheral Blood Lymphocytes of Immuno-related Pancytopenia Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the single nucleotide polymorphism(SNP) of mitochondrial DNA (mtDNA) D-LOOP region in peripheral blood lymphocytes of immuno-related pancytopenia (IRP) patients and its correlation with immune parameters.</p><p><b>METHODS</b>The D-LOOP region in mitochondrial DNA of lymphocytes in peripheral blood mononuclear cells from 43 patients with untreated IRP was detected by polymerase chain reaction(PCR). The PCR products were sequenced by the pros and cons direct sequencing methods. The sequencing results were compared with the revised Cambridge reference sequence (rCRS) and the Polymorphic Sites of Human Mitochondrial Genome Database.</p><p><b>RESULTS</b>Among total of 110 variant positions of D-LOOP region in 43 patients, 62 was SNP sites and 48 was mutation sites, of which 14 were the new mutation sites not yet registered in the database, 516 base variations were observed at 110 positions, the most common variations were base substitutions, among them T/C and A/G was 184/410 and 113/410 respectively. In the 110 variant positions, the high frequency variation sites were 73 and 263 for 43/43,311 for 32/43,310 and 16 224 for 27/43,16 519 for 25/43, 489 and 16 362 for 24/43. By the analysis of mitochondrial DNA D-LOOP polymorphism and related clinical immunology indicators of the patient's lymphocytes, it was found that D-loop in adult patients (age≥ 18 years old) significantly correlated with CD15 IgM, GLYCoACells IgM, CD34CellsIgG, CD34Cells IgM correlation.</p><p><b>CONCLUSION</b>The high frequency of polymorphism exists in mitochondrial DNA D-loop region of lymphocytes in IRPA patients, and was significantly correlates with the autoantibodies in bone marrow mononuclear cells in adult patients, which may be associated with the IRP occurrence.</p>

The combined effects of beta-sheet breaker and hUCMSC on APP transgenic mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effect of combining the injection of beta-sheet breaker H102 with human umbilical cord mesenchymal stem cell (hUCMSC) on APP transgenic mice behavior, P-tau, apoptosis and the expression of relevant enzymes in the brain.</p><p><b>METHODS</b>APP transgenic mice were randomly divided into model group, hUCMSC group, H102 group, H102 with hUCMSC group and a group of C57BL/6J mice with the same age and background was set as normal. After two weeks and four weeks, the ability of spatial reference memory was tested by Morris Water Maze. After four weeks, immunohistochemical stain and Western blot were done to detect the content of Bad, Bax, Bcl-2, Bcl-xl, P-tau, GSK-3beta, PP-2A and PP-1 in mice brain.</p><p><b>RESULTS</b>The ability of memory of hUCMSC in 2 weeks group was slightly improved than that in the model group. hUCMSC in four weeks group, H102 group and H102 with hUCMSC group significantly improved the ability of and memory, and reduced the phosphorylation of tau and brain cell's apoptosis of the Alzheimer disease (AD) mice.</p><p><b>CONCLUSION</b>Beta-sheet breaker H102 together with transplanting hUCMSC is an effective therapeutic strategy for AD.</p>

Glycyrrhetinic acid induces apoptosis and alters survivin gene expression in human myeloma cell line U266 / 中国实验血液学杂志

This study was aimed to investigate the effects of glycyrrhetinic acid (GA) on proliferation, apoptosis and survivin mRNA expression in human myeloma cell line U266 in vitro. Cell proliferation was assayed by MTT method. Both cell apoptosis and cell distribution in cell cycle were analyzed by using flow cytometry. Scanning electron microscopy was used to observe the morphological changes in U266 cells induced by GA. Expression of survivin mRNA was detected by quantitative real-time reverse transcription-polymerase chain reaction. The results showed that GA inhibited proliferation of U266 cells in a time- and dose-dependent manners in vitro. GA presented apoptosis induction potency to U266 cells, obvious changes in morphology of U266 cells was observed under scanning electron microscope. The cells were arrested at the G(0)/G(1) phase, showing the accumulation in G(0)/G(1) phase, reduction of cells in G(2)/M phase and S phase. GA could down-regulate the expression of survivin gene in U266 cells in a dose-dependent manner. It is concluded that GA can inhibit proliferation of U266 cells in a time- and dose-dependent manners and induce apoptosis of this cell line in vitro through arresting G(0)/G(1) phase and down-regulating expression of survivin.

Influence of H102 on the expression of amyloid protein and amyloid precursor protein in the hippocampus of APP695 transgenic mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the influence of H102 on the expression of amyloid protein and amyloid precursor protein in the hippocampus of APP695 transgenic mice.</p><p><b>METHODS</b>The 9-month-old APP695 transgenic mice were randomly divided into the model group and the H102 group; C57BL/6J mice were adopted as normal control group. The H102 group were injected with H102 in a dose of 3 microl/per mouse in lateral ventricle, once a day, for ten days; while the model group and the control group were injected with saline. The hippocampus and temporal cortex of the brain sections from transgenic mice and wild type female mice were subjected to immunohistochemistry and Congo red histological staining, and observed the difference of the protein expression under microscope. The expression of the APP protein was detected by Western blot.</p><p><b>RESULTS</b>Abeta and APP immunohistochemistry showed density of positive cell in the CA1 region of hippocampus of control group were less than model group. H102 peptide reduced the area, and density of positive cells. Congo red staining showed there were lots of amyloid plagues in the brains of model mice but not in the brains of normal control. And the Western blot showed the content of the APP protein of the model group was much higher than the H102 group. H102 significantly decreased the amyloid plagues.</p><p><b>CONCLUSION</b>The expression of APP, Abeta are increased in APP695 transgenic mice, and H102 can decrease the level of APP, Abeta in transgenic mice.</p>

Damage effects of sleep deprivation on myocardium and its antioxygen index in rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of sleep deprivation (SD) on myocardium and its antioxygen index.</p><p><b>METHODS</b>35 Sprague Dawley rats were randomly divided into five groups: Cage control, Tank control, SD 2 d, SD 4 d and SD 6 d. The "flower pot" technique was used to establish rats sleep deprivation model followed by record of surface electrocardiogram, detection of myocardium morphology changes under microscope and transmission electron microscope and investigation of MDA content and SOD activity of myocardial mitochondria.</p><p><b>RESULTS</b>After sleep deprivation, heart rate increased and ECG showed ischemia of myocardium; subcellular organelles such as chromosome, endoplasmic reticulum, mitochondria, intercalated disk impaired, myofibril lysis or necrosis, and lipid peroxidation reaction effects spread widely; edema, bleeding of the microvessels and invasion of the monocytes could be seen in the lumen. The MDA level increased and SOD activity increased followed by a decreased trend.</p><p><b>CONCLUSION</b>Sleep deprivation can induce damage on myocardium, and the stress especially oxygen stress caused by SD may be the possible mechanism.</p>

Modulation with bupleurum root on brain electrical activities in epileptic model / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of bupleurum root on epileptic seizure.</p><p><b>METHODS</b>The rabbits and rats were injected by pilocarpine as epileptic models, and observed the effect of bupleurum on the electroencephalogram (EEG) and hippocampal slice by electroencephalograph and glass microelectrode extracellularly.</p><p><b>RESULTS</b>The seizure time and duration of each major seizure of epilepsy were significantly shortened and the interval of seizure significantly prolonged (P < 0.05) after intraabdominal injection of bupleurum root. After instilling the injection of bupleurum root onto the slices could reduce the amplitude of evoked field potential in epileptic hippocampal slices remarkably, the average of fall is 20.41%, and restore in 6.86 minutes on average (P < 0.001).</p><p><b>CONCLUSION</b>Bupleurum root can inhibit the brain electrical activities in epileptic model, it is suggest that bupleurum has the distinct effect of antiepilepsy.</p>