Research progress in mechanism of curcumin in treatment of Parkinson disease / 中国药理学与毒理学杂志

Curcumin (Cur) is an important bioactive component of polyphenols in the rhizomes of Curcuma longa L., Tulipa gesneriana L. and other Curcuma plants. It has a wide range of pharmacological effects such as anti-tumor, anti-atherosclerosis, anti-inflammatory, and neuroprotection. Parkinson disease (PD) is a neurodegenerative disease that often occurs in the elderly. Its main pathological characteristics are the characteristic loss of substantia nigra dopaminer?gic neurons, the decrease of dopamine content in the striatum, and the formation of Lewy bodies. At present, the main methods of clinical treatment of PD include drug therapy and surgical operation, but due to its complicated pathogene?sis, they can only play a role in relieving, but cannot be completely cured. Modern pharmacological studies have shown that Cur has certain effects in the treatment of PD. ① Anti-oxidative stress: oxidative stress is closely related to the degeneration of dopaminergic neurons. Studies have found that Cur can increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce malondialdehyde (MDA) content, thereby reducing oxidative stress damage and protecting dopaminergic neuron.②Reduce inflammation in brain tissue:neuroinflammation plays an impor?tant role in the development of PD. Reducing the level of inflammatory factors can have a certain therapeutic effect on PD. Studies have shown that high-dose Cur can reduce the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis fac?tor-α (TNF-α) in brain tissue, reduce inflammation, inhibit further neuronal damage, improve learning and memory, and exert neuroprotective effects. ③ Activation of autophagy: the abnormal accumulation of α-Synuclein (α-Syn) in Lewy bodies is closely related to PD, and autophagy dysfunction leads to α-Syn clearance obstacles and an important factor of abnormal aggregation. Cur can increase the expression of microtubule-associated protein 1 light chain 3 (LC3-Ⅱ) and lysosome-associated membrane protein 2A (LAMP2A), and reduce the protein and mRNA expression of α-Syn. It can be seen that Cur promotes the elimination ofα-Syn and protects neurons from damage by activating autophagy.④Inhi?bition of mitochondrial dysfunction:mitochondria plays a central regulatory role in the process of cell apoptosis, and mito?chondrial dysfunction is related to reactive oxygen species, energy and mitochondrial membrane potential, which may cause substantia nigra striatal neuropathy. Experiments have shown that Cur can reduce the active oxygen content in PC12 cells induced by MPP+, maintain the normal membrane potential of mitochondria, thereby stabilizing mitochondrial function and inhibiting PC12 cell apoptosis. This study summarized the action mechanism of Cur in the treatment of PD, and clarified the basis of its pharmacodynamics, providing a reference for the clinical research and new drug develop?ment research of Cur in the treatment of PD.

Hamilton-Thorne Integrated Visual Optical System Ⅰ (IVOSⅠ) versus IVOS Ⅱ for human sperm analysis / 中华男科学杂志

Objective@#To compare the computer-assisted sperm analysis (CASA) systems Hamilton-Thorne Integrated Visual Optical System Ⅰ (IVOSⅠ) and IVOS Ⅱ after verifying the performance of the latter so as to ensure the accuracy of the results of analysis.@*METHODS@#Based on the criteria established in the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen (WHO 5th Ed), we compared the main semen parameters obtained from IVOSⅠ with those generated by IVOS Ⅱ, and examined the consistency between the results of the two sperm analyzers.@*RESULTS@#The linear relationship of the outlier test, bias estimation and scatter plot and the results of the outlier test of the two systems all met the requirements of comparison analysis and showed an obvious correlativity. The application scope of the results obtained from the apparatus indicated a reasonable value range, with r = 0.988 for sperm concentration, r = 0.975 for sperm progressive motility (PR), and r = 0.981 for total sperm motility. Evaluation of the acceptability of the predicted bias showed that the allowable total error (TEa) to be 6.67% with sperm concentration at 12 × 106 /ml and 2.34% with PR < 31%, their upper limit of the allowable error < 1/2. The results of IVOS Ⅱ conformed to the requirements of the WHO 5th Ed.@*CONCLUSIONS@#The main parameters derived from IVOSⅠ and IVOS Ⅱ are comparable and consistent, indicating that both can be used for the examination of semen samples.

Novel Zn-doped CuO nanocomposites inhibit tumor growth in vitro and in vivo:role of reactive oxygen species-dependent apoptosis and autophagy cross-linked by NF-kappaB pathway / 中国药理学与毒理学杂志

OBJECTIVE Zn-doped CuO nanocomposites (nZn-CuO NPs) are novel nanoparticles synthesized by sonochemical method.This study aimed to further investigate the antitumor effects and mechanism of nZn-CuO NPs, as well as the exact mechanism of reactive oxygen species (ROS) on nZn-CuO NPs-induced death using N-acetylcysteine (NAC). METHODS The antitumor effects of nZn-CuO NPs were evaluated by MTS assay and orthotopic transplantation tumor model in nude mice. The effects of nZn-CuO NPs with or without NAC on ROS production, DNA damage, apoptosis, mitochondrial damage, autophagy, lysosome impairment, and ER and Golgi stress were determined. Also,western blot was used to detect apoptosis and autophagy related proteins,as well as NF-κB pathway related proteins. RESULTS nZn-CuO NPs significantly inhibit tumor growth both in vitro and in vivo. nZn-CuO NPs were able to cause cytotoxicity, ROS production, DAN damage mitochondrial damage, apoptosis, and autophagy, and NAC can attenuate them. Further studies showed that nZn-CuO NPs induced changes of apoptosis, autophagy and NF-κB pathway related proteins, and NAC can restore them. CONCLUSION Overall, our data demonstrated that nZn-CuO NPs could inhibit tumor growth both in vitro and in vivo by ROS-dependent regulation of apoptosis and autophagy, which might be cross-linked by NF-κB pathways.

Antitumor activity of extracts from rabbit skins inflamed by Viccinia virus vaccine in vitro / 国际药学研究杂志

Objective To investigate the effect of extracts from rabbit skins inflamed by Viccinia virus vaccine (analgecine) on the proliferation of human cancer cells and on the cytokine secretion in mouse spleen lymphocytes in vitro. Methods Five human tumor cell lines, HepG2, LM3, H460, A549 and HeLa were used and the effect of analgecine (1.63, 0.815, 0.326, 0.163 and0.0815 U/ml) on the cell proliferation was evaluated by the CCK-8 assay. The mouse spleen was isolated aseptically, and the spleen lymphocyte suspension was prepared and cultured with PRMI-1640 medium containing 10％ fetal bovine serum (FBS). For detection of the cytokine IL-2, IFN-γ, IL-4 and IL-12 level, the stimulant concanavalin A (ConA) or lipoplysaccharide (LPS) was added into the lymphocyte suspension, and the lymphocytes were cultured under the presence of analgecine at the final concentration of 0.815, 0.163 and 0.0815 U/ml for 24 hours. Then, the level of the cytokines in the supernatant was detected by the ELISA kit. On the other hand, the effect of supernatant of the spleen lymphocyte cultures under the presence of analgecine at 0.815 U/ml on the proliferation HepG2 cells was also evaluated by the CCK-8 assay. The CCK-8 assay was performed after cultivation of the HepG2 cells in the whole supernatant or in its dilution with fresh medium for 24 hours. Results Analgecine showed a dose-dependent inhibitory effect on the five tested cancer cell lines, with the inhibition rate of 58.95％, 55.08％, 57.28％, 45.80％ and 48.18％ at the 1.63 U/ml on the HepG2, LM3, H460, A549 and HeLa cells, respectively. Compared with the control group, the secretion of IL-2, IFN-γ and IL-4 was significantly increased in the 0.163 and 0.815 U/ml analgecine groups (P＜0.01), while the secretion level of IL-12 was increased in the 0.0815, 0.163 and 0.815 U/ml analgecine groups (P＜0.01). The supernatant of the mouse spleen lymphocyte cultures under the presence of0.163 U/ml analgecine could inhibit the HepG2 cell proliferation in a dose-dependent manner, and the inhibitory effect of the whole supernatant was significantly stronger than the effect of the same concentration analgecine 0.163 U/ml (P＜0.01). Conclusion Analgecine could inhibit the cell proliferation of the tested five human cancer cell lines, increased the secretion of IL-2, IFN-γ, IL-4 and IL-12 cytokines in mouse spleen lymphocytes, all in vitro, and its effect on the cytokine secretion may be related to the inhibitory effect on the human cancer cell proliferation.

Effect of omeprazole on antiplatelet activities of W1 / 国际药学研究杂志

Objective To investigate the antiplatelet effects of candidate drug W1 when combined with omeprazole,respec?tively.Methods The experimental rats were randomly divided into 5 groups:control group,clopidogrel(10 mg/kg)group,clopido?grel(10 mg/kg)+omeprazole(80 mg/kg)group,W1(3 mg/kg)group,and W1(3 mg/kg)+omeprazole(80 mg/kg)group.Four hours after oral administration of the drugs,the rats were measured for their platelet aggregation rate;Western blot was used to deter?mine the protein expressions of P2Y12 receptor,P-Akt and P-Erk.Results For the platelet aggregation rate,compared with the con?trol group,the 4 groups decreased significantly(P<0.01);the platelet aggregation rate in the clopidogrel + omeprazole group in?creased significantly than that in the clopidogrel group(42% and 20.4%,respectively,P<0.01);the platelet aggregoction rate (30.9%)in W1+omeprazole group was significantly higher(P<0.01)than that in the W1 group(20.5%),which was lower than that in the clopidogrel+omeprazole group(P<0.01).For the protein expression detected by the western blotting,there were no signif?icant changes in the expression of P2Y12 receptor on the platelet surface,in the clopidogrel or W1 group in comparison with the clopi?dogrel+omeprazole or W1+omeprazole group,respectively,while the phosphorylation level of Akt and Erk was up-regulated in the clopidogrel+omeprazole or W1+omeprazole group compared with the clopidogrel or W1 group,and the up-ragulatory effect of omepra?zole was weaker in the W1+omeprazole group than that in the clopidogrel+omeprazole group. Conclusion Combined use of omepra?zole could inhibit the antiplatelet activities of clopidogrel or W1,with the inhibitory effect weaker in W1 group than in clopidogrel group,suggesting that the risk for the combination of omeprazole with W1 is likely less than that for the combination with clopidogrel.

Diagnosis and surgical treatment of tight carotid stenosis / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the specialty of diagnosis and surgery of tight carotid stenosis.</p><p><b>METHOD</b>From January 2000 to December 2009, 53 patients with tight carotid stenosis (> 95%) were operated on. All 53 patients had tight carotid stenosis more than 95% on one side in whom 28 had contralateral carotid stenosis or occlusion. The clinical and imaging data as well as surgical outcomes of the patients were retrospectively analyzed.</p><p><b>RESULTS</b>Forty-five patients had postoperatively done well without any complications. There were 3 cases of hemodynamic instability and one case of cardiac ischemia which resolved in one to two days. One patient developed mild hoarseness. One complicated with bacteremia due to deep vein catheter insertion. Two patients experienced brain hemorrhage. None of this series occurred perioperative brain ischemia.</p><p><b>CONCLUSIONS</b>Tight carotid stenosis indicates a need for expeditious carotid endarterectomy with very low rates of brain ischemia. Intraoperative shunting is seldom necessary. Postoperative hyperperfusion syndrome and brain hemorrhage should be worried. Micro-endarterectomy can effectively prevent from restenosis.</p>

The strategy of management for bilateral carotid atherosclerotic stenosis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the indication, time and strategy of surgery for patients with bilateral carotid atherosclerotic stenosis.</p><p><b>METHODS</b>Seventy-four patients with bilateral carotid atherosclecrotic stenosis were admitted to our hospital from February 1987 to December 2007. In 34 patients who presented with unilateral symptoms and underwent ipsilateral carotid endarterectomy (CEA), contralateral CEA or carotid artery stenting (CAS) was performed in 8 because of severe stenosis (> 70%) or unstable plaque. Thirty-eight patients presented with bilateral symptoms. Among them, 15 underwent CEA on both sides, 3 were performed CEA on one side and CAS on the other side, while 20 underwent unilateral CEA only. In 2 asymptomatic patients, CEA was also performed.</p><p><b>RESULTS</b>Ninety-three cases of CEA were performed in 74 patients. Sixty-eight patients were uneventful after operation. Neurological deficits deteriorated in 2 patients. Four patients developed cardiac ischemia, cerebral hemorrhage and hoarseness respectively. Sixty-seven patients were followed-up for 4.9 years. No cerebral ischemia relevant to operated carotid artery developed in 63 patients.</p><p><b>CONCLUSIONS</b>If the indication is obvious, CEA should be performed no matter how contralateral carotid artery is. The strategy of therapy is individual. Whether using shunt depends on intra-operative monitoring.</p>

Protective effect of ischemic preconditioning against cold ischemia and reperfusion injury of rat small intestinal graft / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the protective effect of ischemic preconditioning against cold ischemia and reperfusion injury of rat intestinal graft following orthotopic transplantation.</p><p><b>METHODS</b>Eighty SD rats were randomly assigned into two groups with and without ischemic preconditioning, and each group was divided into 4 subgroups (n=10) according to the intestinal graft cold ischemia time of 3, 6, 12, and 18 h, respectively. Ischemic preconditioning model was established, and the small intestinal graft was preserved at 4 degrees celsius; in Ringer lactate solution for the corresponding time, followed by orthotopic transplantation of the graft. The graft samples were collected for histological examination 1 h after reperfusion, and nuclear factor-kappaB (NF-kappaB) expression in the epithelial cells was detected.</p><p><b>RESULTS</b>Ischemia preconditioning obviously relieved the histological ischemia/reperfusion injury, as shown by regular alignment of the small intestinal villi, alleviated muscular layer edema and decreased expression of NF-kappaB in the epithelia of the graft in groups with cold preservation.</p><p><b>CONCLUSION</b>Ischemic preconditioning can protect the intestinal graft from cold ischemia/reperfusion injury, and NF-kappaB is an important cytokine in ischemia preconditioning.</p>

Changes in the phosphorylation of cAMP response element binding protein in the rat nucleus accumbens after acute and chronic ethanol administration / 生理学报

To define the molecular basis of ethanol dependence, changes in the phosphorylation of cAMP response element binding protein (CREB) in the nucleus accumbens of rats after acute and chronic ethanol administration were detected using immunohistochemistry. The results demonstrate that the expression of phospho-CREB (p-CREB) protein in the rat nucleus accumbens significantly increased after 15 min of acute ethanol exposure, reaching a peak at 30 min after ethanol administration. The increment remained after 1 or 6 h of ethanol exposure compared to the control rats. In contrast, chronic intake of ethanol solution obviously decreased the expression of p-CREB protein compared to the control rats. The decrement remained 24 h or 72 h after ethanol withdrawal, and returned to the control levels after 7 d of ethanol withdrawal. The results suggest that an acute ethanol administration led to an increase in the phosphorylation of CREB in the nucleus accumbens, but chronic ethanol administration produced a decrement, which is possibly one of the molecular mechanisms of alcohol dependence.

High risk factors and management for atrial fibrillation after resection of esophageal or cardiac carcinoma / 中国癌症杂志

Purpose:To investigate the prevention and treatment protocol for Af after resection of esophageal and car- dia carcinoma.Methods:Analyses for clinical materials of 1527 patients underwent resection for esophageal and cardiac carcinoma.Results:There were Af 23 cases.Age older than 60 years,abnormal ECG or/and pulmonary function before operation,gastro-esophageal anastomosis above the aortic arch and histological staging Ⅲ～Ⅳ were risk factors for AF.Fa- tal AF was rarely seen.In our 23 cases after treatment in time AF disappeared.Conclusions:Further recognition for post- operative AF and management of perioperative period complication,may reduce the danger of postoperative AF.