Kangting Ji

Danshen protects endothelial progenitor cells from oxidized low-density lipoprotein induced impairment

In this study, we examined the protective effects of Danshen both on endothelial progenitor cells (EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we randomly divided 24 subjects with hypercholesterolemia into two groups (the control group and the Danshen-treated group). At the end of two weeks of treatment, the EPC cellular functions of both groups were tested. The results indicated that, compared to the control group, EPCs in the Danshen-treated group showed significantly better cellular functions, which was manifested in the cloning number, the proliferation capacity, the number of EPC adhesions, and cell migration. In the subsequent in-vitro experiments, EPCs were treated with vehicle, oxidized low-density lipoprotein (Ox-LDL, 100 µg/ml), or Ox-LDL (100 µg/ml) plus different concentrations of Danshen (Danshensu 2, 10, or 50 µg/ml, respectively) for 24 h. The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity (0.24±0.08, 0.37±0.11, 0.30±0.04 vs. 0.13±0.02, P<0.05, P<0.01, and P<0.01, respectively), and adhesion ability (63.00±11.60, 70.00±10.80, 85.50±11.41 vs. 40.50±6.85, all P<0.01). Compared to the group treated with Ox-LDL alone, Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde (MDA) [(4.34±0.54), (3.98±0.47), (3.46±0.31) vs. (5.57±0.64) nmol/ml, all P<0.01], increased the production of superoxide dismutase (SOD) [(29.74±0.71), (31.09±0.83), (30.41±0.65) vs. (14.76±3.99) U/ml, all P<0.01], and lowered the expression of interleukin-6 (IL-6) [(24.62±7.69), (27.04±3.14), (33.38±18.86) vs. (230.67±33.53) pg/ml, all P<0.01] and tumor necrosis factor-α (TNF-α) [(41.72±6.10), (17.02±6.82), (3.73±2.26) vs. (228.71±41.53) pg/ml, all P<0.01] in Ox-LDL treated EPCs. These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.

Ox-LDL induces dysfunction of endothelial progenitor cells via activation of NF-κB.

Dyslipidemia increases the risks for atherosclerosis in part by impairing endothelial integrity. Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. Oxidized low-density lipoprotein (ox-LDL) can induce EPC dysfunction, but the underlying mechanism is not well understood. Human EPCs were cultured in endothelial growth medium supplemented with VEGF (10 ng/mL) and bFGF (10 ng/mL). The cells were treated with ox-LDL (50 µg/mL). EPC proliferation was assayed by using CCK8 kits. Expression and translocation of nuclear factor-kabba B (NF-κB) were evaluated. The level of reactive oxygen species (ROS) in cells was measured using H2DCF-DA as a fluorescence probe. The activity of NADPH oxidase activity was determined by colorimetric assay. Ox-LDL significantly decreased the proliferation, migration, and adhesion capacity of EPCs, while significantly increased ROS production and NADPH oxidase expression. Ox-LDL induced NF-κB P65 mRNA expression and translocation in EPCs. Thus ox-LDL can induce EPC dysfunction at least by increasing expression and translocation of NF-κB P65 and NADPH oxidase activity, which represents a new mechanism of lipidemia-induced vascular injury.

Shengmai injection, a traditional chinese patent medicine, for intradialytic hypotension: a systematic review and meta-analysis.

Intradialytic hypotension (IDH) is a global public health problem. A rising number of IDH sufferers resort to Chinese patent medicine, Shengmai Injection (SMI) in China. The objectives of present study are to assess the effectiveness and safety of SMI as an adjunct therapy for IDH. A systematic search of 6 medical databases was performed up to December 2011. Randomized trials involving SMI adjuvant therapy versus conventional therapy were identified. RevMan 5.0 was used for data analysis. Ten randomized clinical trials with 437 participants were identified. Methodological quality was considered inadequate in all trials. Compared with conventional therapy, SMI adjunct therapy showed significant effects in improving the clinic effective rate (P < 0.01), decreasing the incidence of IDH episode (P < 0.01), decreasing the frequency of nursing interventions (P < 0.01), and increasing diastolic blood pressure (P < 0.01). There was no statistical significance in the improvement of mean arterial pressure (P = 0.22) and systolic blood pressure (P = 0.08) between two groups. Four studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, SMI adjunct therapy appears to be potentially effective in treatment of IDH and is generally safe. However, further rigorous designed trials are needed.

Relation between Age-Related Macular Degeneration and Cardiovascular Events and Mortality: A Systematic Review and Meta-Analysis

Data on the association between age-related macular degeneration (AMD) and cardiovascular disease and mortality are conflicting. The purpose of this report is to conduct a systematic review to better understand the role of AMD as a risk factor for CVD events and mortality. We searched Medline (Ovid) and Embase (Ovid) for trials published from 1980 to 2015. We included 20 cohort studies that reported relative risks with 95% confidence intervals for the association of AMD and cardiovascular events and mortality, involving 29,964,334 participants. In a random-effects model, the adjusted RR (95% confidence interval [CI]) associated with AMD was 1.08 (1.00–1.117) for all-cause mortality (8 studies) and 1.18 (0.98–1.43) for cardiovascular disease mortality (5 studies). The pooled RR (95% CI) was 1.17 (0.94–1.45) for coronary heart disease (CHD; 3 studies) and 1.13 (0.93–1.36) for stroke (8 studies). Findings from this systematic review support that AMD is associated with increased risk of all-cause mortality. The evidence that AMD predicts incident CVD events or CVD mortality remains inclusive and warrants further study in the future.

Exploration of the mechanisms by which 3,4-benzopyrene promotes angiotensin II-induced abdominal aortic aneurysm formation in mice

OBJECTIVE This study examined the influence of 3,4-benzopyrene (BaP), a compound found in cigarette smoke, on the formation of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) formation in mice and the underlying mechanisms. METHODS C57/B6n mice were divided into four groups. The control group received a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II/BaP group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal BaP injection (10 mg/kg, dissolved in medium-chain triglycerides). The BaP group received a weekly intraperitoneal BaP injection (10 mg/kg). After 5 weeks, abdominal aortic diameter was determined. Aortic tissues underwent hematoxylin and eosin, Masson, and immunochemistry staining for evaluation of vascular wall structure, collagen, macrophage infiltration, matrix metalloproteinases (MMPs), and apoptosis. RESULTS The Ang II infusion and BaP injection induced AAAs in 41.67% of mice vs 25% in the Ang II group (P < .05). The average aortic diameter increased in the Ang II/BaP group compared with the Ang II group (1.40 ± 0.25 vs 1.2 ± 0.23 mm; P < .05). Average aortic muscular cell apoptosis was higher in the Ang II/BaP group (31% ± 12%) than in the Ang II (19% ± 5%; P < .05) or BaP groups (23% ± 4%; P < .05). Aortic macrophage infiltration and expression of MMP-2, MMP-9, MMP-12, and nuclear factor-κB increased (0.56 ± 0.12, 0.47 ± 0.13, 0.49 ± 0.14, 0.49 ± 0.11, and 0.42 ± 0.12, respectively) in the Ang II/BaP group compared with the Ang II group (0.27 ± 0.08, 0.25 ± 0.06, 0.24 ± 0.09, 0.24 ± 0.09, and 0.23 ± 0.06, respectively; P < .05 for all). CONCLUSIONS BaP promotes Ang II-induced AAA formation in mice via elevating infiltration of macrophages, activating nuclear factor-κB, upregulating the expression of MMP-2, MMP-9, and MMP-12, and increasing the apoptosis of vascular muscle cells in its synergistic effect with Ang II in aortic wall.

The protective effect of astragaloside IV against benzo[a]pyrene induced endothelial progenitor cell dysfunction.

AIMS Benzo[a]pyrene (BaP), a prominent component of tobacco, has been revealed to induce damage to endothelial progenitor cells (EPCs). Astragaloside IV (AS-IV) is widely used for the treatment of cardiovascular diseases in China. In this study, we evaluated the effects of AS-IV on the function of human EPCs after BaP exposure and explored the underlying mechanism. MATERIALS AND METHODS Human umbilical cord blood mononuclear cells were isolated using density gradient centrifugation. Cells of the 4th passage were randomly divided into 6 groups. EPCs of experimental groups were pre-treated with different concentrations (2, 10 and 50 μg/mL) of AS-IV for 2h before exposure to BaP (20 μM) for 24h. The proliferation, migration, and adhesion of the treated EPCs were evaluated using a cell counting kit-8, Transwell assay and adhesion assay respectively. Interleukin-1β, tumor necrosis factor-α, malondialdehyde and SOD contents in the supernatant were evaluated. The expression of RAGE protein was measured by Western blotting. KEY FINDINGS The results demonstrated that AS-IV pre-treatment significantly improved BaP-induced dysfunction of EPCs in terms of proliferation, migration and adhesion. Furthermore, AS-IV reduced the production of reactive oxygen species, malondialdehyde, interleukin-1β and tumor necrosis factor-α of the BaP-treated EPCs. Finally AS-IV pre-treated EPCs showed an increased SOD activity and decreased RAGE protein expression. SIGNIFICANCE AS-IV is able to prevent BaP-mediated EPC dysfunction by at least inhibiting oxidative stress through the RAGE pathway.

Relation of phosphodiesterase type 5 inhibitors and malignant melanoma: a meta-analysis and systematic review

Data on the association between using PDE5 inhibitors and malignant melanoma are conflicting. To estimate the relation of using PDE5 inhibitors with risk of malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up to February 2017, and a random effects model was used to calculate the summary risk estimates. Five observational studies were included. Five studies reports encompassed a total of 15,979 melanoma cases occurring among 1, 188,414 participants. The pooled multivariable-adjusted RR of melanoma in patients with using PDE5 inhibitors was 1.12 (95% CI: 1.03–1.21, I2 = 0.48). Findings from this systematic review support that PDE5 inhibitor use is associated with increased risk of melanoma in ED patients, the result remains inclusive and warrants further study in the future.

Factors associated with decision time for patients with ST-segment elevation acute myocardial infarction

Increased delay in visiting a hospital for patients with ST-segment elevation myocardial infarction (STEMI) is often associated with poor outcomes. The factors associated with the decision time were analyzed by comparing the characteristics of patients with delays longer or shorter than the median of 60 min. Pre-hospital delay tended to be longer for patients living in suburban areas compared to those in urban areas (P=0.015). Shorter decision time was more likely among older patients. Being married, medical insurance coverage, and the level of educational qualification did not affect decision time. More efforts should be paid to educate the patients with high risk in suburban areas in order to effectively reduce pre-hospital delays.

Significance of Aquaporin (AQPs) expression in the prognosis of Gastric Cancer

Gastric carcinoma is one of the most lethal malignancy at present with leading cause of cancer-related deaths worldwide. Aquaporins (AQPs) are a family of small, integral membrane proteins, which have been evidenced to play a crucial role in cell migration and proliferation of different cancer cells including gastric cancers. However, the aberrant expression of specific AQPs and its correlation to detect predictive and prognostic significance in gastric cancer remains elusive. In the present study, we comprehensively explored immunohistochemistry based map of protein expression profiles in normal tissues, cancer and cell lines from publicly available Human Protein Atlas (HPA) database. Moreover, to improve our understanding of general gastric biology and guide to find novel predictive prognostic gastric cancer biomarker, we also retrieved ‘The Kaplan–Meier plotter’ (KM plotter) online database with specific AQPs mRNA to overall survival (OS) in different clinicopathological features. We revealed that ubiquitous expression of AQPs protein can be effective tools to generate gastric cancer biomarker. Furthermore, high level AQP3, AQP9, and AQP11 mRNA expression were correlated with better OS in all gastric patients, whereas AQP0, AQP1, AQP4, AQP5, AQP6, AQP8, and AQP10 mRNA expression were associated with poor OS. With regard to the clinicopathological features including Laurens classification, clinical stage, human epidermal growth factor receptor 2 (HER2) status, and different treatment strategy, we could illustrate significant role of individual AQP mRNA expression in the prognosis of gastric cancer patients. Thus, our results indicated that AQP’s protein and mRNA expression in gastric cancer patients provide effective role to predict prognosis and act as an essential agent to therapeutic strategy.

Effects of macrophage migration inhibitory factor on cardiac reperfusion injury in mice with depression induced by constant-darkness

RATIONALE Depression is associated with coronary artery disease and increases adverse outcomes and mortality in patients with acute myocardial infarction, but the underlying pathophysiological mechanisms remain unclear. OBJECTIVE To evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury in mice with constant darkness-induced depression. METHODS AND RESULTS Twenty C57BL/6 mice (8 weeks old, male) were randomly divided into 2 groups: one group was housed in a 12h light/dark cycle environment (LD) and the other in a constant darkness environment (DD). After 3 weeks, constant darkness-exposed (DD) mice displayed depression-like behavior as indicated by increased immobility in the forced swim test (FST) and lower sucrose preference rate. Western blotting revealed cardiac MIF expression was significantly lower in the DD mice than that in the LD mice. Next, 84 mice were randomly divided into 4 groups: LD sham group, LD I/R group, DD sham group, and DD I/R group. Following ischemia and reperfusion, mice in the DD I/R group had a larger infarct area and lower heart function index than mice in the LD I/R group (P < 0.05 for both). The cardiac pAMPK and pACC expression levels of the DD I/R group were also lower in the DD I/R group (P < 0.05). CONCLUSION DD-induced depression might cause decreased expression of MIF in the heart, resulting in downregulation of MIF-AMPK signaling and a subsequent adverse outcome after a cardiac I/R injury.