The aim of this study is to investigate the effect and mechanism of angiotensin (Ang) II on E-selectin and vascular cell adhesion molecule-1 (VCAM-1) expression in rat brain microvascular endothelial cells (BMEC) and evaluate the effect of compound EXP-2528, a novel Ang II type 1 (AT1) receptor antagonist. The experiment was performed in cultured BMEC of rat. The mRNA and protein expression of E-selectin and VCAM-1 in BMEC was analyzed by RT-PCR and Western blotting, respectively. The results showed that the mRNA and protein expression of E-selectin and VCAM-1 in BMEC were significantly upregulated by 4 h or 18 h exposure to 1 x 10(-7) mol x L(-1) Ang II. These effects were abolished by pretreatment with the selective AT1 receptor antagonists losartan and compound EXP-2528, but not with the AT2 selective antagonist PD123319. Combining losartan with PD123319 also significantly inhibited Ang II-induced E-selectin and VCAM-1 expression in BMEC, but there was no significant difference compared with losartan group. These findings indicated that Ang II upregulated E-selectin and VCAM-1 in BMEC by activating AT1 receptor and then involved in the development of cerebrovascular disease.
Angiotensin II ; pharmacology ; Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Brain ; blood supply ; Cells, Cultured ; E-Selectin ; genetics ; metabolism ; Endothelial Cells ; metabolism ; Imidazoles ; pharmacology ; Isoxazoles ; pharmacology ; Losartan ; pharmacology ; Microvessels ; cytology ; RNA, Messenger ; metabolism ; Rats ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

This study was aimed to explore the effect of bortezomib on proliferation and apoptosis of acute monocytic leukemic cells SHI-1 and the function of Bcl-2 gene family including Bcl2l12, Bcl-2 and Bax in its apoptosis. SHI-1 cells were cultured and treated with bortezomib of different concentrations for different time. MTT assay was used to detect the proliferation and apoptosis, Annexin-V staining, mitochondrial transmembrane potential (DeltaPsim) and DNA aga-rose gel electrophoresis were used to investigate apoptosis of SHI-1 cells. RT-PCR was used to analyze the levels of Bcl2l12, Bcl-2 and bax mRNA in SHI-1 cells treated with bortezomib for 0, 6, 12 and 24 hours. The results showed that bortezomib inhibited the proliferation of SHI-1 cells in time-and doze-dependent manners, the IC(50) at 24 and 48 hours were 54.13 nmol/L and 5.45 nmol/L respectively. Bortezomib could induce apoptosis of SHI-1 cells in time-dependent manner, increase expression of Annexin-V positive cells, decrease DeltaPsim of SHI-1 cells and result in DNA fragmentation and morphologic changes of apoptosis. RT-PCR showed that Bcl2l12 mRNA expression was up-regulated, bcl-2 mRNA expression was down-regulated and bax mRNA expression was not changed obviously. It is concluded that bortezomib inhibits the proliferation of SHI-1 and induces apoptosis in which Bcl2l12 and Bcl-2 gene can be ones of the main genes taking part in.
Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Humans ; Leukemia, Monocytic, Acute ; genetics ; Muscle Proteins ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Pyrazines ; pharmacology ; RNA, Messenger ; bcl-2-Associated X Protein ; genetics

Objective To observe dynamically the response of the retinal ganglion cells (RGCs) following chronic optic nerve compression in cats. Methods Thirty adult cats were randomly divided into 6 groups (n=5): normal control group, sham operation group, 1-week compression group, 2-week compression group, 4-week compression group and 8-week compression group. The chronic optic nerve injury was produced by an inflatable balloon implanted under the optic chiasm. RGCs of all animals were labeled with Dil by retrograde tracing 2 weeks before operation. After each group animals were killed by perfusion, the retina were harvested to observe the pathological changes using the light microscope and electron microscope and the number of RGCs was counted under fluorescence microscope. Results There were three cell layers in normal HE stained retinas of cats with clear limits, named ganglion cell layer, bipolar cell layer and photoreceptor cell layer in sequence from vitreous body to selera. By 4 weeks after optic nerve compression, there were no obvious pathological changes in the retinas, however, at 8 weeks the nuclei of the RGCs became markedly thin, with the larger almost disappearing, and the total thickness of the retinas reduced with the glial cells proliferating. Under electron microscopy, the RGCs of the normal eats had large ovate nuclei with homogeneous karyoplasms. The cytoplasm occupied only small space of the cells, but contained a great of cellular organelle. At 4 and 8 weeks after compression, it was found in the retinal ganglion cells that the components of cytoplasm reduced, the endoplasmic reticulum expanded, the mitochondria was swollen, the vacuole occurred under the plasma membrane, the membrane of nuclei was shrunk and the chromatin was marginated and condensed. The density of the DiI labeled RGCs in the normal group animals ranged from 406 to 527 cells/mm2, with an average of (465±38) cells/mm2 and higher density in the central area than in the peripheral one. The number of the RC, Cs was unchanged by 4 weeks after optic nerve compression, but 8 weeks later, the number declined significantly to (293±32) cells/mm2 by about 37%. Conclusion The RGCs present delayed and secondary degeneration following chronic optic nerve compression, which gives an opportunity to protect the RGCs.

BACKGROUNDFew characteristic changes of linear electroencephalograph (EEG) have been reported in schizophrenia. The aim of the present study was to investigate the changes in temporal-spatial dimensional properties of EEG under different cognitive tasks in patients with schizophrenia.

METHODSEEG was recorded by using EEG-1518K system and mapping system (Nihon Kohden Tomioka Corporation, Japan) in 45 schizophrenic patients and 47 healthy adults (normal control, NC) under five states: eyes closed, eyes open, mental arithmetic test with eyes closed, memory test with eyes open, and number cancellation test. Correlation dimension (D2) and point-wise correlation dimension (PD2) were calculated for all EEG analyses.

RESULTS(1) There were no significant differences of D2 and PD2 between NC and schizophrenic patients under states of eyes open and closed. (2) Compared with NC, schizophrenic patients showed decreased performance of D2 in mental arithmetic test with eyes closed and number cancellation test (mental arithmetic test with eyes closed: Nc 5.9 ± 0.6, Sch 3.0 ± 0.8; number cancellation test: Nc 6.0 ± 0.6, Sch 4.4 ± 0.7; P < 0.05 or P < 0.01). (3) Schizophrenic patients also showed decrease performance of PD2 in mental arithmetic test with eyes closed, memory test with eyes open, and number cancellation test (mental arithmetic test with eyes closed: Nc 6.9 ± 0.7, Sch 4.0 ± 0.8; memory test with eyes open: Nc 6.6 ± 0.8, Sch 5.0 ± 0.9; number cancellation test: Nc 7.1 ± 0.7, Sch 4.8 ± 0.9; P < 0.05 or P < 0.01).

CONCLUSIONSNonlinear dynamic analysis provided a new approach in clinical investigation of EEG signals. It was helpful to further understand the cerebral mechanism in schizophrenic cognitive process.

Adult ; Cognition ; physiology ; Electroencephalography ; Female ; Humans ; Male ; Middle Aged ; Nonlinear Dynamics ; Schizophrenia ; physiopathology

OBJECTIVETo investigate the ability of UCB-derived MSCs to support the expansion of HSCs ex vivo and the possible mechanisms involved in this process.

METHODSHSCs from UCB were co-cultured with UCB-derived MSCs for 14 days, and then the total number of HSCs and colony-forming units (CFU) were detected. Cytokines levels of MSCs supernatant were analyzed using ELISA.

RESULTSThe proliferation rate of HSCs co-cultured with MSCs was significantly higher than that of cultured HSCs alone (P<0.05). Furthermore, the addition of exogenous cytokines to the culture system significantly increased the proliferation rate of HSCs (P<0.05). MSCs had secretion of many cytokines, including GM-CSF, IL-7, IL-8, IL-11, SCF and SDF-1α.

CONCLUSIONUCB-derived MSCs as a feeder layer can be an alternative approach for ex vivo expansion of HSCs, and the cytokines by secreted UCB-MSCs may mediate the supportive role of MSC to HSC proliferation.

Antigens, CD34 ; Cell Proliferation ; Coculture Techniques ; Cytokines ; Fetal Blood ; Humans ; Mesenchymal Stromal Cells

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
Aged ; China ; epidemiology ; Chlorides ; blood ; Coronary Artery Disease ; blood ; diagnosis ; mortality ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Sodium ; blood