Major royal jelly proteins alleviate non-alcoholic fatty liver disease in mice model by regulating disordered metabolic pathways.

Nonalcoholic fatty liver disease (NAFLD), the major cause of global chronic hepatic injury, has obtained increasing attention while the current drug treatment still laid safety hazards. Major royal jelly proteins (MRJPs), the water-soluble proteins enriched in royal jelly (RJ), were applied to study its effects on improving NAFLD in the NAFLD mouse model. Herein, we demonstrated that intaking of 250-500 mg/kg/day MRJPs significantly decreased the rate of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. Next, TOF to MRM ("TM") widely targeted metabolomics (untargeted metabolomics + widely targeted metabolomics) was further used to explore the potential mechanism, and we found that 500 mg/kg MRJPs alleviated lipid metabolism, oxidative stress, and inflammation mainly by regulating the metabolisms of alpha-linolenic acid, linoleic acid, arachidonic acid, and biosynthesis of unsaturated fatty acids. Moreover, by detecting multiple oxidative stress factors and inflammatory cytokines, we found that MRJPs indeed exerted antioxidant and anti-inflammatory effects. Together, we demonstrated that MRJPs could mediate the progress of NAFLD through the "multi-component-multi-target-multi-pathway" mechanism, which could be considered as an ideal functional food in alleviating NAFLD. PRACTICAL APPLICATIONS: Royal jelly (RJ) is a bee product with high nutritional value. Major royal jelly proteins (MRJPs) are water-soluble proteins in RJ. Our research showed that MRJPs significantly ameliorated NAFLD induced by a high-fat diet in mice, suggesting that MRJPs could be used as an active ingredient to help improve NAFLD, which was beneficial for the development of related functional foods and the economic value of RJ. Moreover, the metabolic pathways involved in the ameliorative effect of MRJPs were investigated, which provided new ideas for the prevention and treatment of NAFLD.

[Protective effect of cold autologous blood cardioplegic solution on the heart of infants with cyanotic congenital heart disease].

OBJECTIVE: To study the protective effect of cold autologous blood cardioplegic solution on the heart of infants with cyanotic congenital heart disease (CCHD). METHODS: Ninety-six infants with CCHD who underwent cardiopulmonary bypass (CPB) were randomly and equally divided into three groups: histidine-tryptophan-ketoglutarate (HTK) solution, cold non-autologous blood cardioplegic solution, and cold autologous blood cardioplegic solution. The right auricular tissues were taken before aortic cross-clamping and at 30 minutes after aortic declamping, and ATP level and energy charge (EC) in the myocardium were measured. Venous blood was collected before and immediately after CPB, and the serum levels of creatine kinase (CK)-MB and cardiac troponin I (cTnI) were measured. The clinical parameters, such as the re-beat time and re-beat rate during CPB, cardiac index, dependence on positive inotropic agents, and left ventricular ejection fraction (LVEF) at 2 hours after CPB, the incidence rate of arrhythmia within 24 hours after CPB, and postoperative complications and mortality, were recorded. RESULTS: At 30 minutes after aortic declamping, the three groups showed significantly decreased ATP and EC levels (P<0.05), and the cold autologous blood group had significantly higher ATP and EC levels than the other two groups (P<0.05). Immediately after CPB, the three groups showed significantly increased serum levels of CK-MB and cTnI (P<0.05), and the cold autologous blood group had significantly lower serum levels of CK-MB and cTnI than the other two groups (P<0.05). The cold autologous blood group had significantly better outcomes than the other two groups in terms of the re-beat time during CPB and the dependence on positive inotropic agents and LVEF at 2 hours after CPB (P<0.05). CONCLUSIONS: Cold autologous blood cardioplegic solution is superior to HTK and cold non-autologous blood cardioplegic solutions in preserving myocardial energy and reducing myocardial injury in infants with CCHD who undergo CPB, thus providing a better protective effect on the heart.

The circulating level of endothelial progenitor cells after transcatheter closure of congenital heart disease in children.

Data have shown that circulating endothelial progenitor cells (EPCs) closely correlate with the vascular endothelial layer state. The present study was designed to describe the evolution of EPCs in children before and 24 h after transcatheter closure surgery for occluding congenital heart disease. Three groups of patients were studied: the transcatheter closure of atrial septal defect (ASD) group (group 1), the transcatheter closure of patent ductus arteriosus (PDA) group (group 2), and the transcatheter closure of ventricular septal defect (VSD) group (group 3). The circulating EPC level was detected using flow cytometry measuring CD34 and kinase insert receptor double-positive mononuclear cells. The concentration of vascular endothelial growth factor (VEGF) was assessed by enzyme-linked immunosorbent assay. The fluoroscopy time was correctly recorded during the surgery. All of the data were collected before and 24 h after surgery. EPC level and VEGF concentration did not change significantly before and at 24 h after surgery in groups 1 and 2. In group 3, the level of circulating EPCs and VEGF concentration increased significantly 24 h after surgery. The fluoroscopy time in group 3 was significantly longer than in groups 1 and 2. The increased volume of EPCs and VEGF were positively correlated in group 3. Our results showed that transcatheter closure of PDA and ASD in children does not lead to increased circulating level of EPCs. Transcatheter closure of VSD may result in vascular endothelium injury as indicated by increased circulating EPC level.

[Effects of intravenous immunoglobulin and aspirin treatment on the functions of circulating endothelial progenitor cells in children with Kawasaki disease].

OBJECTIVE: To study the effects of intravenous immunoglobulin (IVIG) and aspirin treatment on the functions of circulating endothelial progenitor cells (EPCs) in children with Kawasaki disease (KD) and possible mechanisms. METHODS: Blood samples were obtained in 10 children with KD before and 7 days after the treatment by IVIG and aspirin. MTT method, modified Boyden chamber method and cell culture plate adhesion method were used to assess the functions of EPCs, including proliferation, adhension and migration activities. The plasma levels of tumor necrosis factor-α (TNF-α) and high-sensitivity C reactive protein (hs-CRP) were also measured. RESULTS: The functions of circulating EPCs 7 days after IVIG and aspirin treatment were significantly improved. IVIG and aspirin treatment significantly reduced plasma TNF-α and hs-CRP concentrations. There was a significant linear regression relationship between the reduced plasma TNF-α and hs-CRP levels and the increased functions of circulating EPCs. CONCLUSIONS: IVIG and aspirin treatment can improve the functions of circulating EPCs, possibly through reducing plasma concentrations of TNF-α and hs-CRP.

The functions of endothelial progenitor cells were significantly improved after treatment with intravenous immunoglobulin and aspirin in children with Kawasaki disease.

We sought to determine the effects of treatment with intravenous immunoglobulin (IVIG) and aspirin on the functions of endothelial progenitor cells (EPCs) in patients with Kawasaki disease (KD) as well as its relationship with concentrations of tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP). Ten KD patients in the acute phase of their disease were recruited. We investigated EPC functions in children with KD before and after treatment with IVIG and aspirin. In vitro assays were used to measure the functions, including proliferation, adhesion, and migration activities, of EPCs. Plasma levels of TNF-α and hs-CRP were also assessed. All of the data were assessed before and at 7 days after treatment initiation. EPC functions after 7 days of treatment with IVIG and aspirin were significantly improved than they were before treatment with IVIG and aspirin. Treatment with IVIG and aspirin significantly decreased TNF-α and hs-CRP concentrations. There was a significant linear regression relationship between decreased plasma TNF-α levels, hs-CRP levels, and increased functions of circulating EPCs. The results of our study indicate that the functions of circulating EPCs improved after treatment with IVIG and aspirin, which may be related to decreased concentrations of TNF-α and hs-CRP.

[Decreased circulating endothelial progenitor cell function: relationship with serum concentrations of high-sensitivity C-reactive protein in children with Kawasaki disease].

OBJECTIVE: To study the function of circulating endothelial progenitor cells and its relationship with serum concentrations of high-sensitivity C-reactive protein (Hs-CRP) in children with Kawasaki disease. METHODS: Ten children with Kawasaki disease and ten healthy children as a control group were enrolled. The peripheral mononuclear cells were induced into endothelial progenitor cells using Dulbecco's Modified Eagle Medium containing vascular endothelial growth factor and basic fibroblast growth factor. The proliferative ability, migratory ability and adhesive ability of endothelial progenitor cells were assessed by MTT methods, modified Boyden chamber methods and cell culture plate adhesion method, respectively. The concentrations of serum Hs-CRP were measured by latex enhanced turbidimetric immunoassay. RESULTS: The proliferative ability, migratory ability and adhesive ability of endothelial progenitor cells in the Kawasaki disease group were significantly lower than those in the control group (P<0.01). The serum concentrations of Hs-CRP in the Kawasaki disease group were significantly higher than those in the control group (87.1+/-30.2 mg/L vs 5.3+/-3.4 mg/L; P<0.01). The function of circulating endothelial progenitor cells was negatively correlated with serum concentrations of Hs-CRP in the Kawasaki disease group. CONCLUSIONS: The function of circulating endothelial progenitor cells is decreased in children with Kawasaki disease, which may be associated with the abnormal expression of inflammatory mediators.

[A modified management of the transcatheter occlusion of patent ductus arteriosus: using angiography combined with transthoracic echocardiography].

OBJECTIVE: To evaluate the feasibility of angiography combined with transthoracic echocardiography (TEE) as a modified management of the transcatheter occlusion of patent ductus arteriosus (PDA). METHODS: Forty children with PDA were randomly divided into two groups (n=20 each): observed and control. The control group accepted traditional transcatheter occlusion, and the observed group received a modified management (angiography combined with TEE). The children in the observed group were monitored by realtime TTE. RESULTS: A complete occlusion was acquired by one occlusion operation in each child in the observed group. The TTE demonstrated that the occlusion device was in place, and that the blood flow velocities in the left and right pulmonary artery and the descending aorta were in normal ranges. There were shorter X-ray exposure time, shorter recovering time and less ICU stay time in the observed group than in the control group. The complications associated with blood vessel puncturation occurred in four children from the control group, but none of the observed group had the complications. The total hospitalization cost in the observed group was less than in the control group. CONCLUSIONS: Angiography combined with TEE as a modified management of the transcatheter occlusion of PDA is recommended.

The number and function of circulating endothelial progenitor cells in patients with Kawasaki disease.

Kawasaki disease (KD) is associated with coronary artery injury. Studies have shown that the endothelial progenitor cell (EPC) participates in the process of arterial repair. Data have been reported that the number of EPC increased significantly in the subacute phase of KD. However, until now, there are no data about the functions of EPC in KD patients. The present study was designed to further investigate the number and functions of EPC in KD. Ten KD patients in the acute phase and ten healthy volunteers were recruited and attributed to the KD group and control group, respectively. The circulating CD34/kinase insert domain-containing receptor double positive cells were evaluated in the two groups using flow cytometry. In vitro assays were used to measure the functions of EPC, including proliferation, adhesion, and migration activities. The plasma levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein (hs-CRP) were also assessed in both groups. The number of EPC in the KD group was significantly higher than that of the control group (0.021 +/- 0.007% vs. 0.014 +/- 0.003%, P < 0.05). The migratory response of EPC was significantly decreased in the KD group, compared with that of the control group (5.50 +/- 1.78 vs. 3.40 +/- 1.35 cells/high power field, P < 0.01). Similarly, the proliferative and adhesive activities of EPC in the KD group were also decreased (0.47 +/- 0.08 vs. 0.66 +/- 0.07, P < 0.01; 6.5 +/- 2.12 vs. 11.2 +/- 2.04 cells/high power field, P < 0.01). The plasma NO, TNF-alpha, and hs-CRP levels in the KD group were higher than those of the control group (54.10 +/- 11.78 vs. 38.80 +/- 11.10 mumol/l, P < 0.01; 48.20 +/- 7.42 vs. 37.00 +/- 11.12 pg/ml, P < 0.05; 87.10 +/- 30.18 vs. 5.30 +/- 3.37 mg/l, P < 0.01). The number of circulating EPC positively correlated with the level of NO (r = 0.92, P < 0.001), and the functions of EPC negatively correlated with the levels of TNF-alpha and hs-CRP, respectively. In Kawasaki disease, the number of EPC was enhanced and the functions of EPC were attenuated. The two-way regulation of circulating EPC in KD patients may be associated with the disorders of cytokines or messengers in KD patients.