BACKGROUND: Brain ischemia-reperfusion (IR) injury is closely connected with the activity of Kinesin. Previous research believes that reduced activity of Kinesin, a mierotubule based motor protein, is an early mark for nerve cell death induced by brain ischemia. Erigeron breviscapus can prevent brain IR-induced proteinase C activation, reduce calcium overload, and reduce ischemic infarctional volume, thus attenuating brain IR injury. However, it still remains less reported at present whether the neuroprotective role of erigeron breviscapus is related to Kinesin activity.OBJECTIVE: To observe the effect of erigeron breviscapus on the activity of Kinesin, a microtubule based motor protein, in hippocampal pyramidal cells during brain IR.DESIGN: Randomized controlled study.SETTING: Anesthesia Department, Affiliated Hospital of Jining Medical College; Anesthesiology Key Laboratory, Affiliated Hospital of Xuzhou Medical College.MATERIALS: This experiment was carried out in the Anesthesiology Key Laboratory, the Affiliated Hospital of Xuzhou Medical College, between February and August 1999. Totally 35 male gerbils were included.METHODS: Gerbils were randomized into sham-operation group (n=5), ischemia-reperfusion control group (n=15) and erigeron breviscapus group (n=15), the latter two of which were further divided into three subgroups according to reperfusion time, namely reperfusion group Ⅰ (reperfusion of 6 hours), reperfusion group Ⅱ (reperfusion of 48 hours) and reperfusion group Ⅲ (reperfusion of 96 hours) with 5 in each subgroup. Gerbils in IR group and erigeron breviscapus group were subjected to IR model preparation before experiment by brain arterial occlusion for 10 minutes, while gerbils in sham-operation group had only bilateral common carotid artery isolated without occlusion. Gerbils in erigeron breviscapus group were pretreated 15 minutes before ischemic inducement with intraperitoneal injection of breviscapine (its effective component is erigeron breviscapus) at a dosage of 45 mg/kg, which was replaced with the same volume of isometric normal saline in sham-operation group and IR group. IHC staining was used to detect hippocampus microtubule based motor protein-Kinesin activity with the assistance of computer imaging analysis technology. MAIN OUTCOME MEASURES: Activity and changes of Kinesin of animals in each group.RESULTS: Totally 35 animals were enrolled in this experiment and all entered the result analysis with no one lost during the experiment. In hippocampal CA1 region, Kinesin activity in IR group was found to descend to 58%, 38% and 12% respectively of that in sham-operation group at IR 6 hours, 48 and 96 hours (P < 0.01). In erigeron breviscapus group at IR 6 hours, 48 hours and 96 hours it was 81%, 61% and 21% of that in shamoperation group, and was obviously higher than that in IR control group (P < 0.05). However, the changes of Kinesin activity were not obviously different in hippocampal CA2, CA3 and CA4 regions.CONCLUSION: Erigeron breviscapus can exert brain-protecting function by reducing hippocampal CA1 Kinesin activity during brain IR injury.

AIM: To evaluate expression of the components of endothelin system in pulmonary tissue in a canine pacing-induced congestive heart failure model. METHODS: Twenty-one dogs were divided into 3 groups received 2 (pacing 2 group) or 4 weeks (pacing 4 group) rapid right ventricular pacing, respectively, whereas the other group consisted of 7 dogs received sham-operation as control group. Haemodynamic parameters were detected via left and right heart catheterization. Plasma endothelin-1 was determined by means of RIA. In addition, RT-PCR was used to quantify expression of mRNA of components of endothelin system using ?-actin as internal control. One-way ANOVA and linear regression analysis were used for statistical study. RESULTS:Plasma endothelin-1 increased significantly in heart failure animals. The ratio of preproET-1 to ? actin mRNA was significantly increased from 0.14?0.06 in control group to 0.35?0.08 in pacing 2 group and 0.53?0.08 in pacing 4 group ( P

0.05). In the non-smoking group, the pulse pressures of patients with coronary heart disease were significantly higher than those of subjects with negative angiographic results. Among the three subgroups with different severity of coronary arterial lesion, the pulse pressure of 3-vessel diseases was higher than those of both 2-vessel and 1-vessel subgroup. The pulse pressure of subjects with negative angiographic results in smoking group was significantly higher than that in non-smoking group [(56.1?17.2) mm Hg vs (50.9?11.4) mm Hg,1 mm Hg=0.133 kPa P

AIM: To investigate the changes of intrarenal endothelin system in the course of congestive heart failure. METHODS: A canine congestive heart failure model induced by rapid right ventricular pacing was used in the present study. Twenty-one mongrel dogs divided randomly into 3 groups: control, congestive heart failure 2 weeks(CHF2) and congestive heart failure 4 weeks (CHF4). The severity of heart failure was evaluated by means of hemodynamic measurement. The concentration of plasma endothelin was detected via RIA, and the expression of endothelin was detected by RT-PCR. RESULTS: The concentration of plasma endothelin in both of CHF2 and CHF4 elevated significantly. In CHF2, the expression of endothelin receptor B(ETB) in renal medulla increased significantly. And in CHF4, the expression of preproendothelin, endothelin receptor A(ETA) and ETB increased both in renal cortex and medulla. Furthermore, in cortex, the expression of ETA increased more significantly than ETB, while in medulla, ETB expressed much more than ETA. CONCLUSION: The changes of renal endothelin system expression plays a role in the regulation of water and electrolyte balance during the progress of congestive heart failure.

AIM:To investigate the effects of ox-LDL on TLR2 and TLR4 expression and production of TNF-?,IL-10,IL-12,NO and MDA in macrophages and to observe intervention effect of GW1929 in above procedure.METHODS:The mouse peritoneal macrophages were pretreated with ox-LDL(50 mg/L,100 mg/L)and GW1929(20 ?mol/L)respectively for 24 h.The concentrations of MDA,NO-2/NO-3,TNF-?,IL-10 and IL-12 in the culture fluid were detected.Flow cytometry was used to observe TLR2 and TLR4 expressions after the mouse peritoneal macrophages were pretreated with ox-LDL(50 mg/L)and GW1929(20 ?mol/L)respectively for 6 h,12 h,and 24 h.RESULTS:The concentrations of MDA,NO-2/NO-3,TNF-? and IL-10 in ox-LDL(50 mg/L,100 mg/L)group were higher than those in control and GW1929 group obviously,but the concentrations of above index in ox-LDL(50 mg/L,100 mg/L)+GW1929 group were lower than those in ox-LDL(50 mg/L,100 mg/L)group apparently.No IL-12 in every group was detected.Expressions of TLR-2 in ox-LDL+GW1929(6 h,12 h,24 h)group were lower than those in ox-LDL(6 h,12 h,24 h)group respectively.TLR-4 expressions in ox-LDL+GW1929(12 h)were lower than those in ox-LDL(12 h)apparently.CONCLUSION:ox-LDL up-regulates TLR2 and TLR4 expressions and promotes the production of ROX,NO,TNF-? and IL-10 in macrophages.GW1929 is capable of inhibiting the above ox-LDL effects.

Objective: Diagnostic efficacy of serum markers is low for heart failure patients with preserved left ventricular ejection fraction (HF-pEF) as compared to heart failure patients with reduced left ventricular ejection fraction.We sought to explore the diagnostic value of serum levels of soluble ST2 (sST2) combined with interleukin-33 (IL-33) for the diagnosis of HF-pEF in this study. Methods: A total of 376 patients with HF-pEF (HF group), 376 matched-control patients without heart failure who shared similar clinical characteristics (non-HF group) were included in the study.Another 500 healthy individuals were recruited for assessing the normal ranges of IL-33 and sST2.Serum levels of NT-proBNP were measured by chemi-luminescence assay, while IL-33 and sST2 were measured by enzyme linked immunosorbent assay. Results: Serum levels of IL-33 and sST2 were not normally distributed in healthy population.Serum concentrations of IL-33 and sST2 were significantly higher in HF-pEF patients than in patients in non-HF group (median, IL-33: 0.437 μg/L vs. 0.127 μg/L, P<0.01; sST: 0.118 μg/L vs. 0.067 μg/L, P<0.01). The area under receiver operating characteristic curve (AUC) of sST2 for detecting HF-pEF was 0.763 (95%CI 0.729-0.795, P<0.01), with 71.01% sensitivity and 66.75% specificity, the AUC was 0.884 (95%CI 0.859-0.908, P<0.01), with 80.05% sensitivity and 81.91% specificity in patients with serum IL-33 higher than 0.117 μg/L (median level of serum IL-33 in healthy individuals, n=306). The AUC of NT-proBNP for detecting HF-pEF was 0.83, with 74.73% sensitivity and 84.57% specificity.The AUC of sST2 for detecting HF-pEF was significantly higher than NT-proBNP in population with high serum IL-33 (AUC: 0.88 vs. 0.83, P<0.01). Conclusion Serum sST2 could serve as a satisfactory biomarker for HF-pEF diagnosis, especially for patients with high serum IL-33 concentrations.

ObjectiveTo explore the correlation between serum albumin levels and coronary artery calcification （CAC） in patients with early-stage chronic kidney disease （CKD）， as well as the value of serum albumin levels in predicting the incidence and severity of CAC. MethodsThe study included 391 early-stage CKD patients who underwent coronary computed tomography angiography （CTA） at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2019 and December 2022. Demographic and biochemistry data， as well as the coronary CTA results， were collected. Based on the coronary artery calcification score （CACS）， all patients were divided into non-CAC group （CACS=0， n=184） and CAC group （CACS>0， n=207）. All patients were further divided into 3 groups based on the serum albumin levels： group A （serum albumin levels<35 g/L， n=30）， group B （35 g/L≤ serum albumin levels< 40 g/L， n=198） and group C （serum albumin levels≥ 40 g/L， n=163）. Univariate and multivariate binary logistic regression analyses were conducted to investigate the association between serum albumin levels and CAC in early-stage CKD patients. Differences in CAC among groups were analyzed by using post-hoc multiple comparisons and ordinal logistic regression model analysis. ResultsPatients with CAC had significantly lower serum albumin levels than those without CAC （P<0.05）. There was a negative correlation between serum albumin levels and CACS in early-stage CKD patients （P<0.01）， as serum albumin decreased in levels， CAC increased in severity. ConclusionsOur study shows that early-stage CKD patients with lower serum albumin levels have a higher incidence of CAC. Low serum albumin level is an independent risk factor for CAC progression.

BACKGROUNDAtherosclerosis is a kind of disease with multiple risk factors, of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and development. The aim of this study was to determine the effects of short-term intensive atorvastatin (IA) therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short-term intensive statin therapy.

METHODSAfter exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively, treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent vasorelaxation function were, respectively, measured. mRNA and protein expression of CRP, TNF-α, IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5-lipoxygenase (5-LO) were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes.

RESULTSHFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction, including imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage infiltration into adipose tissue. Five-day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET-1; and improve endothelial function and macrophage infiltration without significant changes in blood lipids. However, all of the above were not observed in LA therapy. In vitro experiment found that lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5-LO in cultured adipocytes, which could be attenuated by short-time (6 hours) treatment of high-dose (5 µmol/L) but not low-dose (0.5 µmol/L) atorvastatin. In addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC, a potent and direct 5-LO inhibitor) could significantly downregulate the above-mentioned gene expression in LPS-treated adipocytes.

CONCLUSIONShort-term IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, which may be partly due to attenuating inflammation of PCAT through inhibiting 5-LO pathway.

Adipose Tissue ; drug effects ; immunology ; Animals ; Arachidonate 5-Lipoxygenase ; metabolism ; Atorvastatin Calcium ; Heptanoic Acids ; therapeutic use ; Hyperlipidemias ; drug therapy ; immunology ; Inflammation ; drug therapy ; immunology ; Lipid Metabolism ; drug effects ; Male ; Pyrroles ; therapeutic use ; Rabbits