Therapeutic effects of a single injection of human umbilical mesenchymal stem cells on acute and chronic colitis in mice.

Multiple injections of bone marrow mesenchymal stem cells (BMMSCs) have been used for treatment of chronic colitis in mice. We aimed to report the therapeutic effects of a single injection of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute and chronic colitis. Male C57BL/6JNarl mice were divided into control, phosphate-buffered saline (PBS), and hUCMSCs treated groups, respectively. Acute and chronic colitis were induced in the mice (except controls) using 3% dextran sulfate sodium (DSS). The mice in the hUCMSCs group underwent a single injection of hUCMSCs. The disease activity index (DAI), colon length, histology, colon inflammation score, in vivo stem cells images, and blood cytokine levels were recorded. The DAI was significantly higher in the hUCMSCs group than in the control group and lower than in the PBS group on all days. The colon length was significantly longer and the colon inflammation score was significantly lower in the hUCMSCs group than in the PBS group on days 8 and 25. IL17A, Gro-α, MIP-1α, MIP-2, and eotaxin were significantly lower in the hUCMSCs group than in the PBS group on days 8 and 25. Single-injection hUCMSCs improved DSS-induced acute colitis and decreased progression of acute colitis to chronic colitis.

BMP4/Id2 signaling pathway is a novel therapeutic target for late outgrowth endothelial progenitor cell-mediated endothelial injury repair.

BACKGROUND: Endothelial progenitor cells (EPCs) play a pivotal role in endothelial repair following artery injury, however, the molecular mechanism of late outgrowth EPCs (LEPCs) in endothelial repair remained to be studied. Bone morphogenetic protein 4 (BMP4) is involved in vascular injury-mediated mobilization and homing of LEPCs. Here, we investigated the influence of BMP4-modified signaling pathway in LEPC-related endothelial repair of human and underlying molecular mechanism. METHODS AND RESULTS: In vitro, after a 28day culture, human LEPCs were pretreated with different concentrations of recombinant BMP4 (0, 10, 50, or 100ng/mL), which markedly augmented the migration and adhesion in vitro and demonstrated a significantly accelerated in vivo endothelial repair capacity of human LEPCs after transplantation into nude mice with carotid artery denudation injury. Moreover, the main Id gene (Id2), a well-characterized down-streaming target of BMP4, upregulated in LEPCs incubated with recombinant BMP4. The BMP4-induced enhancement in in vitro functional activities and in vivo endothelial repair capacity of human LEPCs were abolished by pretreatment with BMP antagonist Noggin or shRNA-mediated knockdown of BMP4 expression. Furthermore, BMP4 gene transfer remarkably activated BMP4-mediated signaling pathway and facilitated therapeutic endothelial repair capacity of LEPCs, and the improved functional activities of human LEPCs could be inhibited by Noggin. CONCLUSION: Thus, the present study demonstrates for the first time that BMP4-related signaling pathway is essential with endothelial repair capacity of LEPCs in human. The upregulation of BMP4-modified signaling pathway in human LEPCs may be a novel therapeutic strategy for endothelial repair after injury.

Efficacy and safety of Yirui capsule in patients with hyperlipidemia: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Hyperlipidemia is a common disease in China. Although 88.9 % of the Chinese population taking lipid-lowering medications has already used a statin, only 61.5 % of the population has reached the goal of low-density lipoprotein cholesterol. Thus, many patients in China seek help from Traditional Chinese Medicine. Yirui capsules are an innovative Chinese Medicine which are designed to improve the blood lipid state in patients with hyperlipidemia. However, there is still a lack of high-quality evidence from clinical trials to support the application. Therefore, we designed a clinical trial to evaluate the safety and efficacy of Yirui capsules for use by patients with hyperlipidemia. METHODS/DESIGN: This is a multicenter, randomized, double-blinded, placebo-controlled trial. Based on lifestyle modification therapy, eligible patients will randomly be assigned to the Yirui capsule or the placebo group. The primary outcome is the percentage of participants who reach the goal of 30 % low-density lipoprotein cholesterol decline at treatment end-point. The secondary outcomes include the changes from baseline to treatment endpoint in low-density lipoprotein cholesterol, total cholesterol, triglyceride, high-density lipoprotein cholesterol, apolipoprotein A, apolipoprotein B, non-high-density lipoprotein cholesterol, MOS 36-Item Short-Form Health Survey scoring, total and individual item scoring of symptomatic grading and quantifying scale, and body mass index. DISCUSSION: The main ingredients of the Yirui capsule are perilla oil, Folium Ginkgo (Yinxingye), Radix Salviae miltiorrhizae (Danshen), Fructus Crataegi (Shanzha), Rhizoma Alismatis (Zexie), and Radix Notoginseng (Sanqi), which are expected to improve the blood lipid state. This randomized placebo-controlled trial will comprehensively evaluate the effectiveness and safety of Yirui capsules against hyperlipidemia in the hope of providing a new adjunctive Chinese medicine option for clinical practice in dyslipidemia treatment. TRIAL REGISTRATION: ChiCTR-IOR-15006496 . Registered on 29 May 2015. PROTOCOL VERSION: WXJ.YRJN-HBT-V1.0 (21 Jan 2015).

Long-term beta blockers for stable angina: systematic review and meta-analysis.

OBJECTIVES: To assess the effects of long-term beta blockers in patients with stable angina. METHODS: We reviewed the literature up to June 2010 from CENTRAL, MEDLINE, EMBASE, CBM, and CNKI for randomized controlled trials. The appropriate data were meta-analysed using Revman 5.0. RESULTS: Twenty-six trials including 6108 patients were identified. The treatment with beta blockers has significantly decreased all-cause mortality when compared with no control (OR 0.40, 95% CI 0.20 to 0.79), but has had no statistically differences when compared with placebo (OR 0.92, 95% CI 0.62 to 1.38) and with calcium-channel blocker (CCB) (OR0.84, 95% CI 0.49 to 1.44). This was similar in patients with fatal and non-fatal acute myocardial infarction when compared with placebo (OR 0.82, 95% CI 0.57 to 1.17) or CCB (OR 1.08, 95% CI 0.71 to 1.66); on revascularization and quality of life. The beta blockers reduced the incident of unstable angina compared to no treatment (OR 0.14, 95% CI0.07 to 0.29), but increased unstable angina compared to placebo (OR 3.32, 95% CI 1.50 to 7.36). There was a significant reduction of nitrate consumption when beta blockers were compared with CCBs (OR 1.18, 95% CI 1.54 to 0.82),but not with placebo and trimetazidine. There was no significant difference in angina attack between each group. Side effects in beta blocker were similar with ones in controls. CONCLUSIONS: Beta blockers may decrease the death and unstable angina when compared with no treatment, but no more effective than other anti-anginal agents on prophylaxis of myocardial ischaemia in stable angina patients.

[A study of effects of impaired glucose tolerance on ventricular remodeling].

OBJECTIVE: To evaluate the effects of impaired glucose tolerance (IGT) on ventricular remodeling. METHODS: Parameters of every subject including left ventricular mass (LVM), left ventricular mass index (LVMI), E/A ratio, 75 g oral glucose tolerance test (OGTT), ambulatory blood pressure monitoring (ABPM) data including 24-hour mean systolic blood pressure (mSBP) and 24-hour mean diastolic blood pressure (mDBP) were collected. Then the relationship of IGT and myocardial remodeling related parameters were analyzed. RESULTS: The rate of diastolic dysfunction was higher in the IGT combined with hypertensive group (74%) compared with the hypertensive group (39%) (χ(2) = 6.5, P < 0.05). The rate of diastolic dysfunction was higher in the IGT group (34%) compared with the normal group (10%) (χ(2) = 5.2, P < 0.05). The rate of Left Ventricular Hypertrophy (LVH) in the IGT combined with hypertensive group (24%) was higher than the other three groups (Hypertension group 7%, IGT group 0, Normal group 0) (χ(2) = 4.56 1, P < 0.05), and there was no significance between the rest three groups (P > 0.05). Stepwise multiple regression showed age and 2 Hours' Postprandial Blood Glucose were independent risk factors of E/A ratio. CONCLUSIONS: These results suggested that IGT is a possible contributor to left ventricular hypertrophy and diastolic dysfunction, and is one of the histopathology of left ventricular remodeling.

Percutaneous intratumoral injection of traditional Chinese herbal compound medicine Star-99 in treatment of hepatocellular carcinoma of mice.

BACKGROUND: Unresectable hepatocellular carcinoma (HCC) lacks effective therapy and entails very poor progress. In 1991, we found that Chinese herbal compound Star-99 has potentially effect on HCC. The purpose of this study was to probe the anti-cancer effect and the mechanism of focal injection of Chinese herbal compound Star-99 into HCC of mice. METHODS: In 32 nude mice transplanted with human hepatocellular carcinoma SMMC-7721, 16 received hypodermic implant and the other 16 orthotopic liver transplant. They were randomly divided into three groups: Star-99 group (Chinese herbal compound, 16 mice), alcohol group (8) and saline group (8), respectively. Intratumoral injection of Star-99, alcohol and saline was carried out 10 days after transplantation of HCC. Twenty days after the first injection, the nude mice were killed after being injected every 5 days with a total of 4 injections in each mouse. Tumor tissues were examined pathologically or via an electron microscope and flow cytometrical (FCM) DNA analysis. The three diameters of the tumor were measured with high-frequency ultrasound before and after injection, and the growth index was calculated with the following formula: volume of tumor (after treatment-before treatment)/volume of tumor (before treatment). Double-blind method was applied in the experiment. RESULTS: The growth index of the Star-99 group (0.068+/-0.022) and the alcohol group (0.079+/-0.024) was markedly lower than that of the saline group (4.345+/-1.453, P<0.01), but there was no significant difference between the Star-99 and alcohol groups. Coagulation (8/8) was the major pathological change in the alcohol group. In the Star-99 group, however, the phenomenon of lymphocytes attacking cancer cells could even be seen under the electron microscope. The typical apoptosis cells and apoptosis bodies as well as the collagen fibrae lined in mass could also be seen in the group (14/16). FCM DNA analysis showed that the rate of apoptosis in the Star-99 group (93.8%) was significantly higher than that in the alcohol (12.5%) and saline groups (12.5%) (P<0.01). CONCLUSIONS: This study shows that Star-99 markedly inhibits and destructs hepatocellular cancer cells. Star-99 is effective to directly destroy the membrane, cytoplasm and nuclei of tumor cells, causing their crumbling, activate the immune function and inflammatory reaction of nude mice, and induce the apoptosis of cancer cells. The effect of Star99 is significantly different from that of alcohol that mainly causes coagulation of cancer cells. Star-99 is feasible in the treatment of HCC.