[Effects of irisin on lipid in mice and glycolipid metabolism in obese mice induced by diet].

Objective: To explore the role of low-dose irisin in the browning of white adipose tissue (WAT) and activation of brown adipose tissue (BAT) in mice, and its effect on the metabolic function of diet induced obesity. Methods: A total of 22 C57/BLKS/J male mice fed with normal diet and 8 fed with high fat diet were separately divided into experimental and control group. The experimental group was given irisin (0.8 ng/g, 200 µl), while the control group was given the same volume (200 µl) of phosphate buffer saline every day for 14 consecutive days intraperitoneally. Food intake and body weight of mice were collected regularly every day. After intervention, the mice were killed and the changes of lipid content and activity in adipose tissue were detected by histopathology and immunohistochemistry. The effects of irisin at different concentrations (0, 20 and 40 nmol/L) on primary white adipocytes and brown adipocytes were evaluated by immunohistochemistry on uncoupling protein 1(UCP1). In order to further evaluate whether irisin has the function of improving metabolism, the changes of serum indexes and hepatic steatosis in mice fed with high-fat diet were monitored. Results: The primary white and brown adipocytes derived from mice were successfully cultured and identified in vitro. In NCD mice, the weight gain of mice with irisin was lower than that of control mice [(-0.78±0.98) vs (0.27±0.55) g]. Histopathology showed that the area of white adipocytes with irisin was smaller than controls [(14.78±8.44) vs (29.49±12.97) µm2] and the brown adipocytes were larger than controls [(0.92±0.35) vs (0.19±0.12) µm2] (both P<0.05), while the expression of UCP1 in both adipose tissues was significantly higher in irisin group. After irisin treatment, the levels of blood glucose [(7.18±0.41) vs (13.48±2.07) mmol/L, P<0.01]and cholesterol [(2.38±0.26) vs (3.89±0.93) mmol/L, P<0.05] were significantly lower than controls, and the content of lipid droplets in liver cells was less than controls [ (2.73±1.96)% vs (14.04±6.29) %, P<0.001]. Conclusions: Low dose irisin can promote the browning of WAT and activate BAT, reducing the body weight of mice by producing heat. Irisin can also effectively improve diet-induced obesity and related metabolic disorders in mice.

[Perioperative outcomes in off-pump coronary artery bypass grafting patients older than 80 years with left ventricular dysfunction or left ventricular normal: a comparative study based on propensity score matching].

Objective: To examine the outcome of off-pump coronary artery bypass (OPCAB) in elderly patients with left ventricular dysfunction. Methods: From June 2008 to July 2016, 252 patients aged over 80 years underwent isolated OPCAB at Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, these patients' data were collected. The left ventricular dysfunction group (ejection fraction (EF): 35% to 50%) was comprised of 31 patients aged (82.0±2.1) years (range: 80 to 88 years), including 25 males and 6 females. Through matching one-to-one on propensity scores, 31 patients (EF>50%) were included into the left ventricular normal group. Among them, there were 25 males and 6 females, aged (81.9±1.9) years (range: 80 to 89 years). Postoperative mortality and complications between the matched groups were compared using the t test, Wilcoxon rank-sum test, χ(2) test or Fisher exact test. Results: Between the dysfunction group and normal group, the preoperative serum creatinine was 144.6(66.0) µmol/L vs. 94.9(43.2) µmol/L (M(Q(R)), Z=3.177, P=0.033), respectively, while the pre-discharge serum creatinine was 147.0(59.0) µmol/L vs. 92.0(24.0) µmol/L (Z=-2.685, P=0.007), respectively. In dysfunction group, the perioperative intra-aortic balloon counterpulsation (IABP) utilization rate was higher (25.8%(8/31) vs. 3.2%(1/31), P=0.026), the total hospitalization day was longer (17(15) days vs. 14(8)days, Z=2.054, P=0.012), the preoperative hospitalization day was longer too (7(7) days vs. 5(4) days, Z=-2.457, P=0.014). However, there was no significant difference in the incidence of postoperative mortality (9.7%(3/31) vs. 3.2%(1/31), P=0.612) and other prognostic indicators between the two groups. Conclusions: The elderly patients, with light and moderate left ventricular insufficiency, are characterized by the abnormal increase in renal function and the rise of IABP utilization due to hemodynamic disorder in OPCAB perioperative period. Preoperative treatment for cardiac insufficiency may be the cause of prolonged preoperative and total hospital stay. However, there is no significant difference in the postoperative mortality and other complications compared with the patients of normal left ventricular function.

[The clinical observation of serum specific biomarkers in patients with chronic graft-versus-host disease].

Objective: Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment. Methods: The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray. Results: Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) . Conclusion: The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.

VEGF Trapon inhibits tumor growth in papillary thyroid carcinoma.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many disease. Angiogenesis from thyroid cancer cell plays the important roles in post-surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). Vascular endothelial growth factor (VEGF) Trapon is a newly developed VEGF-blocking agent with stronger affinity and broader activity than the anti-VEGF antibody bevacizumab. In this study, we tested the activity of VEGF Trapon on a PTC model in vivo. MATERIALS AND METHODS: BC-PAP (derived from papillary carcinomas) transfected with a luciferase-expressing vector were injected into the back to mice. I.p. treatment with VEGF Trapon or control protein (25 mg/kg twice weekly) was started shortly after tumor injection to prevent tumor development (prevention model) or after established tumors were formed to inhibit tumor growth and metastasis formation (intervention model). RESULTS: In the prevention model, VEGF Trapon inhibited tumor growth by 73 ± 12% compared with control (p = 0.014) and significantly prolonged survival. In the intervention model, VEGF Trapon inhibited tumor growth by 68 ± 7% (p < 0.01). Microvascular density was reduced by 56% due to VEGF Trapon treatment (p < 0.01). CONCLUSIONS: VEGF Trapon is a potent inhibitor of BC-PAP tumor growth, angiogenesis and blocks the biological function of VEGF in vivo. These results support further clinical development of VEGF Trapon for PTC and other cancer types.

Human umbilical cord blood-derived stromal cells: a new resource in hematopoietic reconstitution in mouse haploidentical transplantation.

OBJECTIVE: Our previous study showed that human umbilical cord blood-derived stromal cells (hUcBdSCs) expanded CD34(+) cells in vitro. This study further explored the role of hUcBdSCs in vivo. METHODS: The cultured hUcBdSCs were infused into transplanted haploidentical mice to observe hematopoietic recovery and complications. RESULTS: The engraftment was faster in transplantation with hUcBdSCs than without hUcBdSCs. The numbers of fibroblast (CFU-F), granulocyte/monocyte (CFU-GM), erythrocytic (CFU-E), and megakaryocyte (CFU-Mg) colony-forming units were greater among mice transplanted with hUcBdSCs than without hUcBdSCs. The scoring of graft-versus-host disease was significantly lower in mice that had been subjected to transplantation with hUcBdSCs than without hUcBdSCs. The infused hUcBdSCs migrated to the bone marrow of the recipients. CONCLUSIONS: These data indicated that hUcBdSCs improved hematopoietic reconstitution in haploidentical transplantation in mice.

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings.

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.

Cloning of primary human tumors in capillary tube versus Petri dish: a head-to-head comparison.

Plating efficiencies (PEs) of primary human tumors cloned in a capillary assay system were compared to those derived from the conventional two-layer agar Petri dish assay system. A total of 143 consecutively received primary human tumors of 24 different pathologies were simultaneously tested in both assay systems. The successful clonal growth rate in the capillary assay was 82.7%, while in the Petri dish it was 64.7% (p less than 0.001). The median PE was 0.017% in the capillary assay demonstrating a 4.25-fold increase over the 0.004% PE of the Petri dish system. The data confirmed previous results showing that cancer cells of ovarian, breast, and lung origins clone with higher PE in capillary tubes. In contrast, we confirmed that stomach carcinoma cells were the only tumor type that showed a higher PE with the Petri dish method. In addition, this study shows for the first time that lymphomas and renal cell carcinoma, when they survive in vitro, clone equally well in both methods. However, the capillary cloning method resulted in a 66% success rate for lymphoma cell cloning, but Petri dish cloning resulted in only a 33% success rate. Thus, for some types of cancers (i.e., lymphoma), capillary cloning may be advantageous because it improves the probability of obtaining evaluable results. In other cases, the advantage of capillary cloning may be only the decreased amount of specimen and reagents needed for the assay.