Synergistic antitumor effect of HSP90 inhibitor P7 combined with docetaxel in triple-negative breast cancer / 基础医学与临床

Objective To evaluate the effect of docetaxel(DTX)combined with a heptapeptide(LPLTPLP, namely P7)on the human triple-negative breast cancer cell line MDA-MB-231 in vitro.Methods The cell viability was measured by SRB assay followed by evaluation of their combination effect using the isobologram.Flow cytometry was performed to quantify apoptotic cells following treatment of DTX,P7 and DTX combined with P7 and the ex-pressions of the apoptosis-related proteins were determined by Western blot analysis.Results P7 synergized with DTX in cell viability detection.The apoptotic rate was highly increased with increasing Bax /Bcl-2 ratio after MDA-MB-231 cells were exposed to DTX and P 7 combination.Conclusions Combination of P 7 and DTX has synergistic effects on MDA-MB-231 cells characterized by increasing apoptosis activation,in which the expression of pro-apop-totic protein Bax increased with a decline in apoptotic protein Bcl-2.

Increased expression of Hsp90 in pancreatic cancer and its clinical pathological significance / 基础医学与临床

Objective To explore the expression and meaning of heat shock protein 90 (Hsp90) in pancreatic cancer and its correlation with the occurrence,development and metastasis of the tumor tissues and its influence on prognosis. Methods Via immunohistochemical staining, this study used the commercial tissue chip to determine the expression of Hsp90 in 63 pancreatic cancer resection specimens and their para-cancerous counterparts, which were pathologically confirmed from January 2009 to August 2013. We also analyzed the correlation with patient's clinical parameters by using one-way ANOVA or t test. Results Hsp90 expression in pancreatic cancer tissues was significantly higher than tissue adjacent to carcinoma, and it was associated with histological grade, lymph node metastasis,clinical and TNM phase of pancreatic cancer (P<0.05). Conclusions Hsp90 is highly expressed in pancreatic cancer tissues,and its expression is associated with invasion and metastasis of pancreatic cancer. There-fore,Hsp90 may serves as a prognostic indicator of pancreatic cancer while its high expression may represent poor prognosis of pancreatic cancer patients.

Effects of Guhong Injection on Expression of Vascular Endothelial Growth Factor in Cortex after Cerebral Ischemia-reperfusion in Rats / 中国康复理论与实践

@#Objective To study the effects of Guhong injection on the expression of vascular endothelial growth factor (VEGF) in the cortex 14 days after cerebral ischemia-reperfusion. Methods 30 male Sprague-Dawley rats were divided into sham group (n=6), ischemia group (n=6), aceglutamide injection group (n=6), Honghua injection group (n=6) and Guhong injection group (n=6). The middle cerebral arteries of all the rats were occluded for 2 hours and reperfusion, except the sham group. Drugs were administered once a day 24 hours after reperfusion. The expression of VEGF in cortex was detected with enzyme-linked immunosorbent assay (ELISA) 14 days after reperfusion. Results The expression of VEGF decreased in the ischemia group compared with the sham group (P<0.001), and it increased both in the aceglutamide and Guhong injection groups compared with the ischemia group (P<0.05). Conclusion Guhong injection can significantly increase the expression of VEGF in the cortex 14 days after ischemia-reperfusion, which may be one of the ways for neuro-protection.

Propofol may protect PC12 cells from β-amyloid₂₅₋₃₅ induced apoptosis through the GSK-3β signaling pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are two major pathological hallmarks of Alzheimer's disease. One is the progressive accumulation of beta-amyloid (Aβ) in the form of senile plaques; the other is hyperphosphorylated tau, causing neuronal apoptosis. Some inhalation anesthetics, such as isoflurane and desflurane, have been suggested to induce Aβ accumulation and cause AD-like neuropathogenesis. Whether intravenous anesthetics have similar effects is still unclear. We therefore set out to determine the relationship between propofol and AD-like pathogenesis.</p><p><b>METHODS</b>PC12 cells were cultured in serum-free medium for 12 hours prior to drug treatment. Various concentrations from 5 µmol/L to 80 µmol/L of aggregated Aβ25-35 were added to determine a proper concentration for further study. After exposure to 10 µmol/L Aβ25-35 alone or with 20 µmol/L propofol for 6 hours, PC12 cell viability was determined by MTT assay. Western blotting and immunocytochemical staining were performed to observe the protein expression of the Bcl-2 family, tau phosphorylation at different sites, and tau protein kinases and phosphatases.</p><p><b>RESULTS</b>Aβ25-35 induced a decrease in PC12 cell viability in a dose-dependent manner. Exposure to 10 µmol/L Aβ25-35 for 6 hours resulted in the mild cell survival, accompanied by a decline in Bcl-2, and an increase in phosphorylation of GSK-3β and tau at different sites. Compared with the Aβ25-35 group, cells treated with propofol alone showed no significant difference, while cells co-incubated with propofol and Aβ25-35 showed a significantly higher survival rate (P < 0.01 or P < 0.05). Tau phosphorylation at Ser396, Ser404 and Thr231 and the level of GSK-3β in PC12 cells increased after exposure to 10 µmol/L Aβ25-35. Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation.</p><p><b>CONCLUSIONS</b>These data indicate that propofol may protect PC12 cells from Aβ25-35-induced apoptosis and tau hyperphosphorylation through the GSK-3β pathway, therefore it may be a safer anesthesia for AD and elderly patients.</p>

Effects of ning shen ling granule and dehydroepiandrosterone on cognitive function in mice undergoing chronic mild stress / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS), and to determine the effect of Ning Shen Ling Granule (NSL) and dehydroepiandrosterone (DHEA) on them.</p><p><b>METHODS</b>CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.</p><p><b>RESULTS</b>(1) The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01), and these abnormal changes in behavior were improved in those treated with NSL and DHEA. (2) The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05), but could be restored to the normal level after intervention with NSL or DHEA.</p><p><b>CONCLUSION</b>The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.</p>

Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress / 药学学报

<p><b>AIM</b>To determine whether 7-oxo-dehydroepiandrosterone (7-oxo-DHEA) can reverse the hypoimmunity in BALB/c mice exposed to chronic mild stress.</p><p><b>METHODS</b>A chronic mild stress animal model was established by subjecting BALB/c mice to a stressful regimen arranged in an unpredicted manner for 4 consecutive weeks. Immunological function alternations under chronic mild stress were assessed by lymphocytes proliferative response to mitogens and NK cell lysis activity test.</p><p><b>RESULTS</b>The studies showed the correlation between the state of depression and abnormalities in the immune response, such as a decrease of T lymphocytes proliferative response to Con A and suppression of cytotoxic of NK cell. Meanwhile, significant decrease of T3 and T4 levels was also observed. When stressed mice were daily given 7-oxo-DHEA 15 mg.kg-1, lymphocyte proliferative response and the NK cell activity were significantly enhanced and the decreased levels of T3 and T4 were restored in the stressed mice.</p><p><b>CONCLUSION</b>7-oxo-DHEA can improve the depressive symptoms and hypoimmunity of BALB/c mice induced by chronic mild stress as its parent DHEA.</p>

Progresses in pharmacological action of cerebral σ receptor / 中国药理学通报

σ receptors are particularly abundant in the CNS. σ receptors have been shown to exhibit such a wide variety of actions as modulating glutaminergic, dopaminergic and cholinergic neurotransmission. They also play an important role in maintaining cell growth and proliferation, learning and memory. Recent evidence suggests the possible involvement of σ receptors in the pathogenesis of schizophrenia. More researches are expected to supply new targets for treatment and diagnosis.