Actins ; metabolism ; Animals ; Antigens, CD ; metabolism ; Cadherins ; metabolism ; Carotid Artery Injuries ; metabolism ; pathology ; Endothelium, Vascular ; metabolism ; ultrastructure ; Fluorescent Antibody Technique ; Microscopy, Confocal ; Rats ; Troponin ; metabolism

Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.
Brain ; physiopathology ; Cytokines ; HSP70 Heat-Shock Proteins ; physiology ; Humans ; Inflammation ; pathology ; Neurodegenerative Diseases ; physiopathology ; Neurons ; pathology ; Neuroprotection ; Up-Regulation

Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA.
Antioxidants ; therapeutic use ; Apoptosis ; Diterpenes, Abietane ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Salvia miltiorrhiza ; chemistry ; Stroke ; drug therapy

Objective To observe the effects of dexmedetomidine hydrochloride on the cisatracurium-induced neuromuscular blockade in geriatric, young and middle-aged patients. Methods Forty elderly patients and forty young and middle-aged patients undergoing elective abdominal surgery under general anesthesia were randomly divided into 4 groups ( n=20 each):elderly dexmedetomidine hydrochloride group (group DE),elderly control group (group CE),young and middle-aged dexmedetomidine group (group DY) and young and middle-aged control group (group CY).In groups DE and DY,a loading dose of 0.5 μg?kg-1 dexmedetomidine was intravenously infused over 10 min before induction of anesthesia,respectively,followed by infusion at a rate of 0.4μg?kg-1?h-1 until the end of surgery.Equal volume of 0.9% sodium chloride was given in groups CE and CY.Anesthesia was induced with midazolam,fentanyl,propofol and cisatracurium 0.15 mg?kg-1.Four groups were maintained with infusion of propofol and remifentanil. Neuromuscular blockade was maintained with continuous cisatracurium infusion in the four groups and was monitored with TOF-Watch SX acceleromyography at the adductor pollicis.The onset time,TOF no reaction period,duration of action,the amount of cisatracurium consumption,and the spontaneous recovery index ( T1 25% to 75%) were recorded. Results The four groups were comparable in the demographic data.Intubation conditions,the onset time and recovery index were not significantly different among the four groups. The duration of blockade action in groups DE and DY was ( 61. 1 ± 8.9) min and (53.6±9.3) min,which was significantly longer than that in group CE [(49.9±5.8) min] and group CY [(44.8± 6.4) min] (P<0.01).The duration of blockade action was significantly longer in groups DE and CE than in groups DY and CY (P<0.05).The amount of cisatracurium consumption in groups CE and CY was significantly higher than that in groups DE and DY (P<0.05). Conclusion The neuromuscular blockade is longer and the requirement of cisatracurium is less in elderly patients than in young and middle-aged patients.Continuous infusion of dexmedetomidine hydrochloride can't accelerate the onset time of cisatracurium.But duration of action is prolonged and the amount of cisatracurium consumption is lower in patients with infusion of dexmedetomidine hydrochloride.

Aim To investigate the effect of resveratrol on ROS level and PECAM-1 expression in ox-LDL-stimulated platelets. Methods The expression of PE-CAM-1 , Sirt1 and p38 MAPK phosphorylation in ox-LDL-stimulated platelets was determined by Western blot. The level of ROS was measured by immunofluo-rescence kit. Results ox-LDL induced platelet aggre-gation by 14%, whereas resveratrol inhibited platelet aggregation by 50%. Resveratrol decreased ROS level by 3 . 2 fold and completely suppressed PECAM-1 expression in ox-LDL-treated platelets. Resveratrol re-covered Sirt1 expression in ox-LDL-treated platelets. EX527 ( a Sirt1 inhibitor ) increased ROS level and PECAM-1 expression in ox-LDL-stimulated platelets. Meanwhile, resveratrol also suppressed p38MAPK phosphorylation induced by ox-LDL. Conclusion Resveratrol can inhibit platelet aggregation, decrease ROS production and PECAM-1 expression in ox-LDL-stimulated platelets. The mechanism maybe associated with recovery of Sirt1 expression. Moreover, resveratrol can decrease PECAM-1 expression, which may be linked to abolishing p38MAPK phosphorylation.

Aim To investigate the effect of ginkgolide B on junctional proteins in ox-LDL-stimulated human umbilical vein endothelial cells ( HUVECs) . Methods After incubation with ginkgolide B ( 0 . 2 ,0 . 4 ,0 . 6 g · L-1 ) for 1 h, HUVECs were treated with ox-LDL (0. 1 g·L-1 ) for 4 h. The expressions of JAM-A and Cx43 were analyzed with Western blot and immunofluo-rescence. The effect of ginkgolide B on vascular per-meability was analyzed by Transwell experiments. Re-sults JAM-A and Cx43 expressions increased by 22%and 24% in ox-LDL-treated HUVECs, respectively. Whereas ginkgolide B significantly decreased JAM-A and Cx43 expressions. LY294002, a specific inhibitor of PI3K, suppressed JAM-A and Cx43 expressions in ox-LDL-stimulated cells. Ginkgolide B potently re-duced monocyte migration in ox-LDL-treated cells. Conclusion Ginkgolide B significantly suppresses JAM-A and Cx43 expressions, and reduces monocyte migration in ox-LDL-stimulated cells. This demon-strates that ginkgolide B can improve vascular permea-bility. The mechanism might be associated with the in-hibition of PI3K/Akt signaling pathway.

Objective To observe the effect of exposure of emphysema with intermittent hypoxia on oxidative stress injury of myocardial cells in rats. Methods Sixty male Wistar rats were divided randomly into four experimental groups(each n=15). The normal control group was bred normally. The emphysema group was exposed to cigarette smoke twice a day(once 30 minutes). The intermittent hypoxia(IH)group was exposed to intermittent hypoxia circumstance 8 hours/day,and the emphysema with IH group was exposed to cigarette smoke twice a day (once 30 minutes)and intermittent hypoxia circumstance 8 hours/day. Each group was exposed for 8 weeks. At the beginning of 9 weeks,the blood gas analysis was performed in 5 rats selected randomly from each group,and the rest rats were sacrificed and their hearts and lungs were taken. Under light microscope,the lung tissues stained with hematoxylin-eosin(HE)were examined. The lung pathology and the results of blood gas analysis showed that the emphysema with IH rat model was established successfully. The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)in rat myocardium were measured by enzyme-linked immunosorbent assay(ELISA),and the subunit p22phox mRNA expressions of nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with the normal group, the MDA levels and p22phox mRNA expressions were increased obviously in emphysema group, IH group and emphysema with IH group〔MDA(μmol/g):2.93±0.54, 3.58±0.63, 4.51±0.72 vs. 1.75±0.56, p22phox mRNA:0.043±0.004,0.067±0.015,0.123±0.016 vs. 0.018±0.002,all P<0.05〕,but the activities of SOD were decreased significantly(U/mg:36.07±4.79,33.51±7.12,24.29±5.36 vs. 46.08±5.12,all P<0.05). In emphysema with IH group,the increase of MDA levels and p22phox mRNA expressions and decrease of SOD levels were more remarkable compared with those in emphysema group and IH group(all P<0.05). The expression of p22phox mRNA was positively correlated with MDA level(r=0.734,P<0.001). Conclusion The myocardial tissue oxidative stress injury in rats induced by emphysema with intermittent hypoxia exposure is more serious than that induced by exposure of either emphysema or intermittent hypoxia alone,NADPH oxidase possibly being the important medium of myocardial cell response to oxidative stress.

Sphingolipids, especially ceramide and S1P, are structural components of biological membranes and bioactive molecules which participate in diverse cellular activities such as cell division, differentiation, gene expression and apoptosis. Emerging evidence demonstrates the role of sphingolipids in hepatocellular death, which contributes to the progression of several liver diseases including ischaemia-reperfusion liver injury, steatohepatitis or hepatocarcinogenesis. Furthermore, some data indicate that the accumulation of some sphingolipids contributes to the hepatic dysfunctions. Hence, understanding of sphingolipid may open up a novel therapeutic avenue to liver diseases. This review focuses on the progress in the sphingolipid metabolic pathway with a focus on hepatic diseases and drugs targeting the sphingolipid pathway.
Apoptosis ; Ceramides ; metabolism ; Fatty Liver ; metabolism ; physiopathology ; Humans ; Liver Diseases ; metabolism ; physiopathology ; Lysophospholipids ; metabolism ; Reperfusion Injury ; metabolism ; physiopathology ; Sphingolipids ; metabolism ; Sphingosine ; analogs & derivatives ; metabolism

Adult ; Cell Transformation, Neoplastic ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Keratin-10 ; metabolism ; Male ; Ovotesticular Disorders of Sex Development ; metabolism ; pathology ; surgery ; Teratoma ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

AIMA method of stereotaxic apparatus was employed to damage the nucleus basalis of Meynert, and the effects of Tiao-xinzishen prescriptions on neurotransmitters such as ACh, 5-HT and NE in hippocampus were observed.

METHODSRats were placed on the brain stereotaxic apparatus and received a bilateral lesion of Meynert by IA injection, according to the atlas of Daxinos and Watson. After seven days of lesion, AD rats were selected. Rats were treated with Tiaoxin or/and Zishen prescription for 20 days, respectively. Hippocampus ACh was measured by spectrophotometer and 5-HT and NE by high performance liquid chromatography (HPLC).

RESULTSThe contents of hippocampus ACh, 5-HT and NE of AD rats were significantly increased after the treatment with the three prescriptions, respectively.

CONCLUSIONThese prescriptions had some up regulating effects on hippocampus neurotransmitters in rats, which had already decreased due to dementia.

Alzheimer Disease ; drug therapy ; metabolism ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Hippocampus ; metabolism ; Male ; Neurotransmitter Agents ; metabolism ; Phytotherapy ; Rats ; Rats, Wistar ; Serotonin ; metabolism