The efficacy of mind-body (Baduanjin) exercise on self-reported sleep quality and quality of life in elderly subjects with sleep disturbances: a randomized controlled trial.

OBJECTIVES: To examine the efficacy of a 24-week Baduanjin exercise program on self-reported sleep quality and quality of life in community-dwelling elderly subjects with sleep disturbances. METHODS: Community-dwelling elderly men and women meeting criteria for sleep disturbances (i.e., Pittsburgh Sleep Quality of Index (PSQI) score ≥ 5) were recruited and randomized to a Baduanjin exercise intervention group or a control group. Participants in the intervention group completed five 45-min exercise sessions per week for 24 weeks, while those in control group were instructed to maintain their usual lifestyle behaviors. RESULTS: A total of 139 participants were enrolled and randomized. Sixty-two of 67 participants in the intervention group (response rate of 92.5%) and 57 of 72 participants (response rate of 79.6%) in the control group completed intervention and follow-up. The intervention group reported significant improvements in overall sleep quality after 24 weeks compared with those randomized to control (PSQI endpoint-to-baseline change = - 2.6 ± 4.0 vs. - 0.5 ± 4.2, time × group interaction p = 0.007). Intervention group participants had higher response rates at both week 12 (23.9% vs. 9.7%, p = 0.025) and week 24 (40.3% vs. 15.3%, p = 0.001) when compared with the control group. There was a trend that the intervention group had increased quality of life (The Short Form Health Survey [SF-36] endpoint=tobaseline change 6.3 ± 10.9 vs. 2.2 ± 10.9, time × group interaction p = 0.06) when compared with the control group. CONCLUSIONS: Baduanjin exercise is an effective and feasible approach to improve self-reported sleep quality but less likely the quality of life in community-dwelling elderly men and women with sleep disturbances. TRIAL REGISTRATION: Effect of Baduanjin Exercise on the Elderly's Sleep; http://www.chictr.org.cn/listbycreater.aspx; ChiCTR1800014706, registered 1 January 2018.

Efficacy of omega-3 PUFAs in depression: A meta-analysis.

We conducted this meta-analysis of double-blind randomized placebo-controlled trials to estimate the efficacy of omega-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in the improvement of depression. We applied a systematic bibliographic search in PubMed and EMBASE for articles published prior to 20 December 2017. This meta-analysis was performed using RevMan 5.3 and R 3.4.3, and means and standard deviations were calculated in fixed- or random-effects models based on the results of the Q-test. A sensitivity analysis was also conducted to evaluate the stability of the results, and publication bias was evaluated by a funnel plot and Egger's linear regression analysis. Our search resulted in 180 articles; we analyzed 26 studies, which included 2160 participants. The meta-analysis showed an overall beneficial effect of omega-3 polyunsaturated fatty acids on depression symptoms (SMD = -0.28, P = 0.004). Compared with placebo, EPA-pure (=100% EPA) and EPA-major formulations (≥60% EPA) demonstrated clinical benefits with an EPA dosage ≤1 g/d (SMD = -0.50, P = 0.003, and SMD = -1.03, P = 0.03, respectively), whereas DHA-pure and DHA-major formulations did not exhibit such benefits.Current evidence supports the finding that omega-3 PUFAs with EPA ≥ 60% at a dosage of ≤1 g/d would have beneficial effects on depression. Further studies are warranted to examine supplementation with omega-3 PUFAs for specific subgroups of subjects with inflammation, severity of depression, and the dose response for both EPA and DHA supplementation.

IL (Interleukin)-33 Suppresses Abdominal Aortic Aneurysm by Enhancing Regulatory T-Cell Expansion and Activity.

Objective- Inflammation occurs during the progression of abdominal aortic aneurysm (AAA). IL (interleukin)-33 is a pleiotropic cytokine with multiple immunomodulatory effects, yet its role in AAA remains unknown. Approach and Results- Immunoblot, immunohistochemistry, and immunofluorescent staining revealed increased IL-33 expression in adventitia fibroblasts from mouse AAA lesions. Daily intraperitoneal administration of recombinant IL-33 or transgenic IL-33 expression ameliorated periaorta CaPO4 injury- and aortic elastase exposure-induced AAA in mice, as demonstrated by blunted aortic expansion, reduced aortic wall elastica fragmentation, enhanced AAA lesion collagen deposition, attenuated T-cell and macrophage infiltration, reduced inflammatory cytokine production, skewed M2 macrophage polarization, and reduced lesion MMP (matrix metalloproteinase) expression and cell apoptosis. Flow cytometry analysis, immunostaining, and immunoblot analysis showed that exogenous IL-33 increased CD4+Foxp3+ regulatory T cells in spleens, blood, and aortas in periaorta CaPO4-treated mice. Yet, ST2 deficiency muted these IL-33 activities. Regulatory T cells from IL-33-treated mice also showed significantly stronger activities in suppressing smooth muscle cell inflammatory cytokine and chemokine expression, macrophage MMP expression, and in increasing M2 macrophage polarization than those from vehicle-treated mice. In contrast, IL-33 failed to prevent AAA and lost its beneficial activities in CaPO4-treated mice after selective depletion of regulatory T cells. Conclusions- Together, this study established a role of IL-33 in protecting mice from AAA formation by enhancing ST2-dependent aortic and systemic regulatory T-cell expansion and their immunosuppressive activities.

Study on the adsorption of nitrogen and phosphorus from biogas slurry by NaCl-modified zeolite.

A NaCl-modified zeolite was used to simultaneously remove nitrogen and phosphate from biogas slurry. The effect of pH, contact time and dosage of absorbants on the removal efficiency of nitrogen and phosphate were studied. The results showed that the highest removal efficiency of NH4+-N (92.13%) and PO43--P (90.3%) were achieved at pH 8. While the zeolite doses ranged from 0.5 to 5 g/100 ml, NH4+-N and PO43--P removal efficiencies ranged from 5.19% to 94.94% and 72.16% to 91.63% respectively. The adsorption isotherms of N and P removal with NaCl-modified zeolite were well described by Langmuir models, suggesting the homogeneous sorption mechanisms. While through intra-particle diffusion model to analyze the influence of contact time, it showed that the adsorption process of NH4+-N and PO43--P followed the second step of intra-particle diffusion model. The surface diffusion adsorption step was very fast which was finished in a short time.

Effects of Xuezhikang in patients with dyslipidemia: a multicenter, randomized, placebo-controlled study.

BACKGROUND: Xuezhikang (XZK) is an extract of fermented red yeast rice that has lipid-lowering properties. OBJECTIVE: To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no coronary heart disease. METHODS: A total of 116 adults with baseline non-high-density lipoprotein cholesterol (non-HDL-C) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks. RESULTS: A majority of the patients were white (53.4%) or Asian (37.1%). Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks resulted in statistically significant (P < .001) and clinically meaningful decreases in non-HDL-C (∼24% reduction) and LDL-C (∼27% reduction) compared with placebo. XZK treatment at either dose enabled approximately 50% of subjects to reduce their LDL-C levels by ≥ 30%. Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6% reduction in LDL-C. Significant benefits were also observed across secondary efficacy variables, including total cholesterol (TC), apolipoprotein B (Apo B), triglycerides, HDL-C, the TC/HDL-C ratio, and the Apo B/Apo A-I ratio, at treatment week 8 or 12. XZK was safe and well tolerated. Safety and tolerability profiles were similar across treatment groups. Most adverse events were gastrointestinal. No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase. CONCLUSION: Xuezhikang significantly reduced non-HDL-C and LDL-C, and was well tolerated. Further, longer-term studies in more diverse patient populations are needed to corroborate these findings.

Rosuvastatin enhances angiogenesis via eNOS-dependent mobilization of endothelial progenitor cells.

Circulating endothelial progenitor cells (circEPCs) of bone marrow (BM) origin contribute to postnatal neovascularization and represent a potential therapeutic target for ischemic disease. Statins are beneficial for ischemia disease and have been implicated to increase neovascularization via mechanisms independent of lipid lowering. However, the effect of Statins on EPC function is not completely understood. Here we sought to investigate the effects of Rosuvastatin (Ros) on EPC mobilization and EPC-mediated neovascularization during ischemic injury. In a mouse model of surgically-induced hindlimb ischemia (HLI), treatment of mice with low dose (0.1 mg/kg) but not high dose (5 mg/kg) significantly increased capillary density and accelerated blood flow recovery, as compared to saline-treated group. When HLI was induced in mice that had received Tie2/LacZ BM transplantation, Ros treatment led a significantly larger amount of endothelial cells (ECs) of BM origin incorporated at ischemic sites than saline. After treatment of mice with a single low dose of Ros, circEPCs significantly increased from 2 h, peaked at 4 h, declined until 8 h. In a growth-factor reduced Matrigel plug-in assay, Ros treatment for 5 d induced endothelial lineage differentiation in vivo. Interestingly, the enhanced circEPCs and post-HLI neovascularization stimulated by Ros were blunted in mice deficient in endothelial nitric oxide synthase (eNOS), and Ros increased p-Akt/p-eNOS levels in EPCs in vitro, indicating these effects of Ros are dependent on eNOS activity. We conclude that Ros increases circEPCs and promotes their de novo differentiation through eNOS pathway.

18ß-Glycyrrhetinic acid potently inhibits Kv1.3 potassium channels and T cell activation in human Jurkat T cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice has been extensively used in traditional medicines for treatment of many diseases, including inflammations and immunological disorders. Recent studies have shown that the anti-inflammatory and immunomodulation activities of licorice have been attributed to its active component, glycyrretinic acid (GA). GA consists of two isoforms, 18α- and 18ß-. However, its mechanism remains poorly understood. AIM OF THE STUDY: We compared the effects of two isoforms on Kv1.3 channels in Jurkat T cells and further characterized the inhibition of Kv1.3 channels by 18ß-GA in CHO cells. In addition, we examined the effects of 18ß-GA on Kv1.3 gene expression, Ca(2+) influx, proliferation, as well as IL-2 production in Jurkat T cells. MATERIALS AND METHODS: Whole-cell patch-clamp technique was applied to record Kv1.3 currents in Jurkat T or CHO cells. Real-time PCR and Western blotting were used to detect gene expression. Fluo-4, CCK-8 kit and ELISA kit were used to measure Ca(2+) influx, proliferation, and IL-2 secretion in Jurkat T cells, respectively. RESULTS: Superfusion of 18ß-GA (10-100 µM) blocked Kv1.3 currents in Jurkat T cells, while 18α-GA at the same concentration had no effect. The 18ß-GA induced inhibition had a voltage- and concentration-dependent manner with an IC50 of 23.9±1.5 µM at +40 mV in CHO cells. Furthermore, 18ß-GA significantly inhibited Kv1.3 gene expression. In addition, paralleling Kv1.3 inhibition, 18ß-GA also inhibited Ca(2+) influx, proliferation as well as IL-2 production in Jurkat T cells. CONCLUSION: 18ß-GA blocks Kv1.3 channels, which probably involves its anti-inflammatory and immunomodulation effects.

Aconitine blocks HERG and Kv1.5 potassium channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum has been widely used to treat various diseases in China for a long time. However, improper use of this drug results in severe intoxication. Aconitine (ACO), a diterpenoid alkaloid from aconitum, mainly contributes to cardio-toxic effects of aconitum and has also been commonly known to induce arrhythmias in animal models. However, its pro-arrhythmic mechanisms are not clear. AIM OF THE STUDY: The effects of ACO on HERG and Kv1.5 channels were investigated. MATERIALS AND METHODS: HERG and Kv1.5 channels were expressed in Xenopus laevis oocytes, and the resulting currents were recorded using a two-microelectrode voltage clamp technique. RESULTS: In HERG channels, ACO exhibited a blockade in a voltage- and time-dependent manner. The blockade was enhanced by further activation of currents, which were consistent with an open-channel blockade. In Kv1.5 channels, ACO produced a voltage-, time-, and frequency-dependent inhibition. The blockade was enhanced by higher rates of stimulation, consistent with preferential binding of the drug to the open state. In addition, ACO blocked Kv1.5 and HERG channels in a concentration-dependent manner with an IC(50) of 0.796+/-0.123 and 1.801+/-0.332 microM, respectively. CONCLUSIONS: ACO blocks HERG and Kv1.5 potassium channels in the open state. Blockade of potassium channels, particular the HERG channel, may be one of the important mechanisms of how ACO induces arrhythmias.

Protective effect of Astragalus polysaccharides on ATP binding cassette transporter A1 in THP-1 derived foam cells exposed to tumor necrosis factor-alpha.

Astragalus polysaccharide (APS), the main extract from the traditional Chinese medicinal herb Astragalus membranaceus, has been reported to benefit the treatment of immune-inflammatory diseases and metabolic disorders. In atherosclerotic plaques, proinflammatory cytokines exert adverse effects on lipids thereby aggravating atherosclerosis. Recent evidence shows that tumor necrosis factor-alpha (TNF-alpha) can down-regulate the expression of ATP-binding cassette transporter A1 (ABCA1), which plays a vital role in reverse cholesterol transport and determines the process of atherosclerosis. In the present study, the effects of APS on ABCA1 expression, cholesterol effluent rate and total cholesterol content of THP-1 derived foam cells exposed to TNF-alpha were investigated. Compared with the foam cells exposed to TNF-alpha, ABCA1 expression was promoted in the presence of APS. Consequently the cholesterol effluent rate increased and the total cholesterol content decreased significantly. TNF-alpha could enhance the activity of nuclear factor-kappa B (NF-kappaB) in the foam cells. This effect could be attenuated by APS. These findings suggest that APS could protect ABCA1 against the lesion of TNF-alpha in THP-1 derived foam cells, which may contribute to its antiatherosclerotic properties.

Qiliqiangxin regulates the balance between tumor necrosis factor-alpha and interleukin-10 and improves cardiac function in rats with myocardial infarction.

The study investigated the effects of traditional Chinese drug Qiliqiangxin on cardiac function and the expression of pro/anti-inflammatory cytokines TNF-alpha/IL-10 in rats with myocardial infarction (MI). Rats with MI were randomly divided into drug-treated group (MI-Q) and control group (MI-C) compared with sham-operated group (S). Rats in the MI-Q group were treated with crude drug of oral Qiliqiangxin 24h after operation at the dosage of 4g/kg/day for 4weeks, while in MI-C group and S group were treated with normal saline at the same time. Echocardiography and hemodynamic parameters, histopathologic changes and the expression of myocardial cytokines including TNF-alpha and IL-10 were assessed 4weeks after the drug therapy. The results indicated that rats of the MI-C group exhibited decreased cardiac function and increased ratio of TNF-alpha/IL-10 which principally secreted by myocardium compared with those of the S group and Qiliqiangxin treatment significantly improved cardiac function and histopathologic changes with down-regulated ratio of TNF-alpha/IL-10. These data suggests that Qiliqiangxin may improve cardiac function of rats with MI through regulation the balance between TNF-alpha and IL-10.

Glycyrretinic acid blocks cardiac sodium channels expressed in Xenopus oocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice has been used to treat many ailments including cardiovascular disorders in China for long time. Recent studies have shown that the cardiac actions of licorice have been attributed to its active component, glycyrretinic acid (GA). However, its mechanism remains poorly understood. AIM OF THE STUDY: The effects of GA on the cardiac sodium currents (I(Na)), L-type calcium currents (I(Ca,L)) and hyperpolarization-activated inward currents (I(f)) were investigated. MATERIALS AND METHODS: Human isoforms of wild-type and DeltaKPQ-mutant type sodium channels were expressed in Xenopus oocytes, and the resulting currents (peak and late I(Na)) were recorded using a two-microelectrode voltage-clamp technique. A perforated patch clamp technique was employed to record I(Ca,L) and I(f) from isolated rabbit sinoatrial node pacemaker cells. RESULTS: GA inhibited peak I(Na) (33% at 90 microM) and late I(Na) (72% at 90 microM), but caused no significant effects on I(Ca,L) and I(f). CONCLUSION: GA blocked cardiac sodium currents, particularly late I(Na.) Our findings might help to understand the traditional use of licorice in the treatment of cardiovascular disorders, because reduction of sodium currents (particularly late I(Na)) would be expected to provide protection from Na(+)-induced Ca(2+) overload and cell damage.

Blockade of the human ether-a-go-go-related gene potassium channel by ketanserin.

In the present study, we investigated the inhibitory action of ketanserin on wild-type (WT) and Y652 mutant human ether-a-go-go-related gene (HERG) potassium channels expressed in Xenopus oocytes and the effects of changing the channel molecular determinants characteristics on the blockade with and without ketanserin intervention using standard two-microelectrode voltage-clamp techniques. Point mutations were introduced into HERG gene (Y652A and Y652R) and subcloned into the pSP64 plasmid expression vector. Complementary RNAs for injection into oocytes were prepared with SP6 Cap-Scribe after linearization of the expression construct with EcoR I. Clampfit 9.2 software was employed for data collection and analysis. Origin 6.0 software was used to fit the data, calculate time constants and plot histograms. The results showed that ketanserin blocked WT HERG currents in voltage- and concentration-dependent manner and showed minimal tonic blockade of HERG current evaluated by the envelope of tails test. The IC50 value was (0.38+/-0.04) micromol/L for WT HERG potassium channel. The peaks of the I-V relationship for HERG channel suggested a negative shift in the voltage-dependence of activation after using ketanserin, whose midpoint of activation values (V1/2) were (-16.59+/-1.01) mV (control) vs (-20.59+/-0.87) mV (ketanserin) at 0.1 micromol/L, (-22.39+/-0.94) mV at 1 micromol/L, (-23.51+/-0.91) mV at 10 micromol/L, respectively (P<0.05, n=6). Characteristics of blockade were consistent with an open-state channel blockade, because the extent and rate of onset of blockade was voltage-dependent, increasing at more potentials even in the condition of leftward shift of activation curve. Meanwhile, in the different depolarization duration, the fractional blockade of end-pulse step current and peak tail current at 100 ms duration was significantly lower than that at 400 ms and 700 ms, which indicated that following the channel activation fractional blockade was enhanced by the activated channels. Ketanserin could also modulate the inactivation of HERG channel, which shifted the voltage-dependence of WT HERG channel inactivation curve from (-51.71+/-2.15) mV to (-80.76+/-14.98) mV (P<0.05, n=4). The S6 mutation, Y652A and Y652R, significantly attenuated the blockade by ketanserin. The IC50 value were (27.13+/-9.40) micromol/L and (20.20+/-2.80) micromol/L, respectively, increased by approximately 72-fold for Y652A and 53-fold for Y652R compared to that of WT HERG channel blockade [(0.38+/-0.04) micromol/L]. However, between the inhibitory effects of Y652A and Y652R, there was no significant difference. In conclusion, ketanserin blocks WT HERG currents in voltage- and concentration-dependent manner and preferentially blocks open-state HERG channels. Tyr-652 is one of the critical residues in the ketanserin-binding sites.

[Folate reduces monocyte chemoattractant protein-1 expression in rats with hyperhomocysteinemia].

OBJECTIVE: To investigate effects of supplementation of folate on the expression of monocyte chemoattractant protein-1 (MCP-1) in aortic endothelium and release from peripheral blood mononuclear cells (PBMC) in rats with hyperhomocysteinemia induced by ingestion of excess methionine. METHODS: Thirty male SD rats were randomly divided into 3 groups (n = 10 for each group): control group (Control), high homocysteinemia group (Hhcy), and folate supplementation group (FA). They were fed with nomal diet, normal diet enriched by 1.7% methionine, and normal diet plus 1.7% methionine and 0.006% folate, respectively, for 45 days. The levels of total plasma homocysteine (Thcy) were measured by high performance liquid chromatography and the concentrations of chemokine MCP-1 released from PBMC stimulated by oxidized low density lipoprotein were detected by enzyme immunoassays. The expression of MCP-1 on aortas of rats was detected by immunohistochemistry and Western blot. RESULTS: A high methionine diet for 45 days induced hyperhomocysteinemia. Folate supplementation to high-methionine diet significantly decreased plasma Thcy levels (P < 0.01). The expression of MCP-1 in aortic endothelium and the levels of MCP-1 released from PBMC stimulated by oxidized low density lipoprotein were significantly higher in rats of Hhcy group than in rats of control group (P < 0.05, P < 0.01). During supplementation of folate, normalization of Thcy levels was accompanied by a marked reduction of MCP-1 expression in aortic endothelium and by a significant decrease of MCP-1 released from PBMC stimulated by oxidized low density lipoprotein (P < 0.05, P < 0.01). CONCLUSION: Folate supplementation can prevent an elevation of homocysteine levels in the blood and decrease the expression MCP-1 in aortic endothelium and release of MCP-1 from PBMC in rats with hyperhomocysteinemia.