Growth differentiation factor 11 is involved in isoproterenol­induced heart failure.

The present study aimed to investigate the potential effects of growth differentiation factor 11 (GDF11) on isoproterenol (ISO)­induced heart failure (HF) and identify the underlying molecular mechanisms. A rat model of HF was induced in vivo by intraperitoneally administering ISO (5 mg/kg/day) for 7 days. After 4 weeks following establishment of the HF model, hemodynamic analysis demonstrated that ISO induced a significant increase in the left ventricular end­diastolic pressure and a decrease in the left ventricular systolic pressure and maximum contraction velocity. The plasma levels of myocardial injury markers, including lactate dehydrogenase (LDH), creatine kinase (CK), CK­muscle/brain which were determined using the corresponding assay kits and plasma brain natriuretic peptide which was detected by an ELISA kit, an important biomarker of HF, increased following ISO treatment. Furthermore, levels of GDF11 expression and protein, which were estimated using reverse transcription­quantitative polymerase chain reaction and an ELISA kit in plasma and western blotting in the heart tissue, respectively, significantly increased following ISO treatment. To demonstrate the effects of ISO on GDF11 production in cardiomyocytes, H9C2 cells (a cardiomyoblast cell line derived from embryonic rat heart tissue) were treated with ISO (50 nM) for 24 h in vitro; it was revealed that GDF11 protein and mRNA expression levels significantly increased following ISO treatment. In addition, recombinant GDF11 (rGDF11) administered to ISO­treated H9C2 cells resulted in decreased proliferation, which was detected via a CCK­8 assay, and increased LDH levels and cell apoptosis of cells, which was determined using Caspase­3 activity and Hoechst 33258 staining. Additionally, rGDF11 increased the levels of reactive oxygen species and malondialdehyde due to the upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) following rGDF11 treatment. Conversely, GDF11 knockdown reduced ISO­induced apoptosis by inhibiting oxidative stress injury. The results suggested that GDF11 production was upregulated in ISO­induced rats with HF and in ISO­treated H9C2 cells, and that rGDF11 treatment increased ISO­induced oxidative stress injury by upregulating Nox4 in H9C2 cells.

Effects of Tianmagouteng particles on brain cognitive function in spontaneously hypertensive rats with hyperactivity of liver-yang: A [F-18] FDG micro-PET imaging study.

OBJECTIVE: To collect visualized proof of Tianmagouteng particles (TMGTP) in alleviating cognitive dysfunction and to explore its effects on brain activity in spontaneously hypertensive rats (SHRs) with hyperactivity of liver-yang (Gan Yang Shang Kang, GYSK). METHODS: Sixteen SHRs were randomized into treatment group and non-treatment. The SHR with GYSK was induced by gavaging aconite decoction (10mL/kg at 0.2g/mL). After the SHR models were prepared, the rats in the treatment group were administered TMGTP (10mL/kg) once a day for 14days.The rats in the non-treatment group or normal rats (control group) received an equivalent volume of saline. Morris water maze test was conducted before and after the treatment to observe cognitive function. Fluorine 18-deoxy glucose [F-18]FDG micro-PET brain imaging scans was performed after treatment. Data were analyzed with two-sample t-test (P<0. 001) using SPM2 image analysis software. RESULTS: Compared with the non-treatment group, the escape latency significantly decreased but the frequency of entrance into the target zone significantly increased in the treatment group. Consistent with the alteration of cognitive functions, TMGTP induced strong brain activity in the following sites: right dorsolateral nucleus and ventrolateral nucleus of thalamus, amygdala, left met thalamus, cerebellum leaflets, original crack, front cone crack, loop-shaped leaflets; but deactivation of right medial frontal gyrus, bilateral corpus callosum, hippocampus, and left dentate gyrus. CONCLUSION: TMGTP could alleviate cognitive dysfunction in SHRs with GYSK, which was possibly by inducing alteration of glucose metabolism in different brain regions with corresponding functions.

The difference between Asian and Western in the effect of LDL-C lowering therapy on coronary atherosclerotic plaque: a meta-analysis report.

BACKGROUND: The different effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque between Western and Asian remain to be settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Sep. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. RESULTS: Twenty trials (ten in the West and ten in Asia) were identified. For Westerns, Mean lowering LDL-C by 49.4% and/or to level 61.9 mg/dL in the group of patients with baseline mean LDL-C 123.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.156 mm(3), 95% CI -0.248 ~ -0.064, p = 0.001). LDL-C lowering by rosuvastatin (mean 40 mg daily) could significantly decrease the volumes of CAP at follow up. For Asians, Mean lowering LDL-C by 36.1% and/or to level 84.0 mg/dL with baseline mean LDL-C 134.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.211 mm(3), 95% CI -0.331 ~ -0.092, p = 0.001). LDL-C lowering by rosuvastatin (mean 14.1 mg daily) and atorvastatin (mean 18.9 mg daily) could significantly decrease the volumes of CAP at follow up. CONCLUSIONS: There was a different effect of LDL-C lowering on CAP between Westerns and Asians. For regressing CAP, Asians need lower dosage of statins or lower intensity LDL-C lowering therapy than Westerns.

The effect of position on esophageal structure and function determined with solid-state high-resolution manometry.

OBJECTIVE: To investigate the influence of posture on the anatomy and function of esophageal sphincters using solid-state high-resolution manometry. METHODS: Fifty individuals underwent esophageal manometry with a 36-channel solid-state catheter in the supine and upright positions. The length and pressure of the esophageal sphincters, as well as the esophageal and intra-abdominal lengths of lower esophageal sphincter (LES), were recorded. The residual pressure of the upper esophageal sphincter (UES) and the 4-s integrated relaxation pressure were also measured when the participants swallowed 10 consecutive servings of water (5 mL each). The Bland-Altman plot was used to assess agreement between these parameters in the supine and upright positions. RESULTS: The LES resting pressure was significantly decreased in the upright position compared with the supine position (13.85 ± 5.90 mmHg vs 18.09 ± 7.80 mmHg, P = 0.000). Weaker integrated relaxation pressures were observed when the participants were in the upright position (5.66 ± 3.33 mmHg vs 7.80 ± 3.25 mmHg, P = 0.000). Compared with the supine position, the upright esophageal length was longer (P = 0.004) and the upper border of the LES was lower (P = 0.050) when the individuals were in the upright position. The agreement between the two positions was acceptable for the esophageal length, LES upper border location and LES pressure measurements. CONCLUSIONS: Body position exerts a greater influence on the LES than on the UES. Thus, it is necessary to establish normal values for the LES basal pressure and residual pressure in different positions.

[Effect of electroacupuncture intervention at different time-points of post-modeling on hippocampal monoamine neurotransmitter levels in mice with vascular dementia].

OBJECTIVE: To observe the effect of electrocupuncture (EA) intervention at different time-points of post-modeling on behavior and hippocampal monoamine neurotransmitter noradrenalin (NE), dopamine (DA) and 5-hydroxytrypamine (5-HT) contents in vascular dementia (VD) mice, so as to study its mechanism underlying improvement of VD. METHODS: A total of 60 Kunming mice were randomized into sham-operation control (n = 20), VD model (n = 20), EA-day (D)-1 (EA treatment was given from the 1st day on after modeling, n = 10), EA-D-3 (EA was given from the 3rd day on after modeling, n = 10) groups. VD model was established by occlusion of the bilateral cervical common arteries and reperfusion. EA (2 Hz/80 Hz) was applied to "Baihui" (GV 20), "Dazhui" (GV 14),"Zusanli" (ST 36) and "Geshu"(BL 17) for 10 min, once daily for 15 days. Hippocampal NE, DA and 5-HT contents were assayed by fluorospectrophotometry. The mouse's learning-memory ability was assessed by step-down tests. RESULTS: In comparison with the sham-operation control group, the learning-memory ability (marked increase of reaction time and error times, decrease of step-down latency) was apparently lowered in the model group (P < 0.01). The hippocampal NE, DA and 5-HT contents were significantly lower in the model group than in the sham-operation group (P < 0.01). Compared with the model group, the mice's learning-memory ability (marked decrease of reaction time and error times, increase of step-down latency) was significantly increased in EA intervention groups (P < 0.01), and hippocampal NE, DA and 5-HT levels were significantly increased (P < 0.01), and the effect of EA-D-3 group was obviously better than that of the EA-D-1 group (P < 0.05, P < 0.01). CONCLUSION: EA can improve the VD mice's learning-memory ability, which is closely related to its effects in up-regulating hippocampal NE, DA and 5-HT contents, and the effect of later EA intervention after modeling is better.