Efficacy, safety, and economy of shensongyangxin capsules for the treatment of coronary heart disease arrhythmia: a meta-analysis of randomized controlled trials.

Background: Shensong Yangxin Capsules (SSYX) is a proprietary Chinese medicine commonly, used in the treatment of arrhythmia. In recent years, a flurry of randomized controlled trials of SSYX was reported in the treatment of Coronary heart disease arrhythmia in China. However, these experiments have not been systematically evaluated by economics. The purpose of this study was to assess the efficacy, safety, and economy of the SSYX in the treatment of arrhythmia in patients with coronary heart disease. Methods: With "Shensong Yangxin Capsules" "Coronary Heart Disease" "Coronary Atherosclerotic Heart Disease"and "Arrhythmia" as the subject words, the relevant journals and conference papers were searched manually in China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP, PubMed, Web Of Science, CBM, Embase and The Cochrane Library. The literature of randomized controlled trials of SSYX in the treatment of coronary heart disease arrhythmia was searched until November 2022. All data were analyzed using RevMan 5.3 Sotware and combined with cost-effectiveness for economic evaluation. Results: Twenty randomized controlled trials were included in this study, with a total of 2011 cases. The meta-analysis showed that the therapeutic effect of SSYX-metoprolol is superior to that of metoprolol alone. SSYX is superior to amiodarone in improving the total clinical effective rate, reducing the incidence of adverse reactions, and reducing the junction premature beats. There was no significant difference between the SSYX and amiodarone in the curative effect of ECG, ventricular premature complexes, and atrial premature beats. The results of pharmacoeconomics show that SSYX has a cost-effectiveness advantage in treating coronary heart disease arrhythmia. Single-factor sensitivity analysis also confirmed the stability of the results. In summary, SSYX has a curative effect, safety, and economy in treating coronary heart disease arrhythmia.

Role of circadian clock in the chronoefficacy and chronotoxicity of clopidogrel.

BACKGROUND AND PURPOSE: The role of circadian locomotor output cycles kaput (CLOCK) in regulating drug chronoefficacy and chronotoxicity remains elusive. Here, we aimed to uncover the impact of CLOCK and dosing time on clopidogrel efficacy and toxicity. EXPERIMENTAL APPROACH: The antiplatelet effect, toxicity and pharmacokinetics experiments were conducted with Clock-/- mice and wild-type mice, after gavage administration of clopidogrel at different circadian time points. The expression levels of drug-metabolizing enzymes were determined by quantitative polymerase chain reaction (qPCR) and western blotting. Transcriptional gene regulation was investigated using luciferase reporter and chromatin immunoprecipitation assays. KEY RESULTS: The antiplatelet effect and toxicity of clopidogrel in wild-type mice showed a dosing time-dependent variation. Clock ablation reduced the antiplatelet effect of clopidogrel, but increased clopidogrel-induced hepatotoxicity, with attenuated rhythms of clopidogrel active metabolite (Clop-AM) and clopidogrel, respectively. We found that Clock regulated the diurnal variation of Clop-AM formation by modulating the rhythmic expression of CYP1A2 and CYP3A1, and altered clopidogrel chronopharmacokinetics by regulation of CES1D expression. Mechanistic studies revealed that CLOCK activated Cyp1a2 and Ces1d transcription by directly binding to the enhancer box (E-box) elements in their promoters, and promoted Cyp3a11 transcription through enhancing the transactivation activity of albumin D-site-binding protein (DBP) and thyrotroph embryonic factor (TEF). CONCLUSIONS AND IMPLICATIONS: CLOCK regulates the diurnal rhythmicity in clopidogrel efficacy and toxicity through regulation of CYP1A2, CYP3A11 and CES1D expression. These findings may contribute to optimizing dosing schedules for clopidogrel and may deepen understanding of the circadian clock and chronopharmacology.

Use of network pharmacology and molecular docking to explore the mechanism of action of curcuma in the treatment of osteosarcoma.

Curcuma has been used as an adjuvant treatment for osteosarcoma (OS) due to its anticancer compounds. However, the underlying mechanism remains unclear. Therefore, this study aimed to explore the mechanism of action of curcuma in the treatment of OS using network pharmacology and molecular docking. In this study, anticancer compounds were obtained from relevant literature, and curcuma-related targets and OS treatment targets were obtained from public databases. Protein‒protein interaction networks were constructed to screen out the hub genes using the STRING database and Cytoscape software. Cluster analysis of the protein modules was then performed using the Cytoscape MCODE plugin. Furthermore, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed for common targets among curcuma targets and OS-related targets using the DAVID database. Finally, molecular docking was performed, and the results were verified by Auto dock Tool and PyMOL software. Our research identified 11 potential active compounds, 141 potential therapeutic targets and 14 hub genes for curcuma. AKT1, TNF, STAT3, EGFR, and HSP90AA1 were the key targets closely related to the PI3K/Akt signaling pathways, HIF-1 signaling pathways, ErbB signaling pathways, and FOXO signaling pathways, which are involved in angiogenesis, cancer cell proliferation, metastasis, invasion, and chemotherapy resistance in the microenvironment of OS. Molecular docking suggested that the core compound had a strong affinity for key targets, with a binding energy of less than - 5 kJ/mol. The study showed that curcuma-mediated treatment of OS was a complex process involving multiple compounds, targets, and pathways. This study will enhance the understanding of how curcuma affects the proliferation and invasion of OS cells and reveal the potential molecular mechanism underlying the effect of curcuma on OS lung metastasis and chemotherapy resistance.

Puerariae lobatae radix protects against UVB-induced skin aging via antagonism of REV-ERBα in mice.

Puerariae lobatae radix (PLR) is a wildly used herbal medicine. Here we aimed to assess the PLR efficacy against UVB (ultraviolet-B)-induced skin aging and to determine the mechanisms thereof. We found a significant protective effect of PLR (topical application) on UVB-induced skin aging in mice, as evidenced by reduced skin wrinkles, epidermal thickness, and MDA (malondialdehyde) content as well as increased levels of HYP (hydroxyproline) and SOD (superoxide dismutase) in the skin. In the meantime, Mmp-1, p21 and p53 levels were decreased in the skin of PLR-treated mice. Anti-aging effects of PLR were also confirmed in L929 cells. Furthermore, PLR up-regulated skin expression of BMAL1, which is a known regulator of aging by promoting Nrf2 and antioxidant enzymes. Consistently, Nrf2 and several genes (i.e., Prdx6, Sod1, and Sod2) encoding antioxidant enzymes in the skin were increased in PLR-treated mice. Moreover, based on Gal4 chimeric assay, Bmal1 reporter gene and expression assays, we identified PLR as an antagonist of REV-ERBα that can increase Bmal1 expression. Intriguingly, loss of Rev-erbα protected mice against UVB-induced skin aging and abrogated the protective effect of PLR. In conclusion, PLR acts as an antagonist of REV-ERBα and promotes the expression of BMAL1 to protect against skin aging in mice.

Physicochemical and rheological properties of pomelo albedo pectin and its interaction with konjac glucomannan.

Pomelo albedo was extracted with water to obtain the high methoxyl pectin, labeled as PAP. The physicochemical and rheological properties of PAP were determined. The effects of PAP addition on rheological property and thermal stability of konjac glucomannan (KGM) were evaluated. Results indicated that PAP was composed of arabinose, glucose and galacturonic acid with a relative mass percentage of 7.2%: 9.5%: 83.3%, and exhibited an average molecular weight of 56.6 kDa. The degree of esterification of PAP was 65.5%, showing PAP was a kind of high methoxyl pectin. Apparent viscosity of PAP was concentration-dependently increased, while it was slightly enhanced with salt (NaCl or CaCl2) addition. Moreover, the addition of PAP declined the apparent viscosity, elastic property and thermal stability of KGM. It can be concluded that interaction was occurred between KGM and PAP. Meanwhile, the interaction mechanism between KGM and PAP has been preliminarily proposed. The present study can provide some references for the application of PAP and support the combination usage of this pectin and KGM in food and other industries.

Molecular Mechanism and Health Role of Functional Ingredients in Blueberry for Chronic Disease in Human Beings.

Functional ingredients in blueberry have the best health benefits. To obtain a better understanding of the health role of blueberry in chronic disease, we conducted systematic preventive strategies for functional ingredients in blueberry, based on comprehensive databases, especially PubMed, ISI Web of Science, and CNKI for the period 2008⁻2018. Blueberry is rich in flavonoids (mainly anthocyanidins), polyphenols (procyanidin), phenolic acids, pyruvic acid, chlorogenic acid, and others, which have anticancer, anti-obesity, prevent degenerative diseases, anti-inflammation, protective properties for vision and liver, prevent heart diseases, antidiabetes, improve brain function, protective lung properties, strong bones, enhance immunity, prevent cardiovascular diseases, and improve cognitive decline. The anthocyanins and polyphenols in blueberry are major functional ingredients for preventive chronic disease. These results support findings that blueberry may be one of the best functional fruits, and further reveals the mechanisms of anthocyanins and polyphenols in the health role of blueberry for chronic disease. This paper may be used as scientific evidence for developing functional foods, nutraceuticals, and novel drugs of blueberry for preventive chronic diseases.

Greenhouse wastewater treatment by baffled subsurface-flow constructed wetlands supplemented with flower straws as carbon source in different modes.

Four laboratory-scale baffled subsurface-flow constructed wetlands (BSCWs) were established for the treatment of greenhouse wastewater containing high levels of nitrate and sulfate in the present study. Each BSCW microcosm involved a treatment zone and another post-treatment zone with a surface area ratio of 2:1. Evenly mixed straws of carnation and rose (w/w: 1/1), two common ornamental flowers, were supplemented as an organic carbon source into the treatment zone through a hydrolysis zone (CW 1), decentralized vertically installed perforated pipes (CW 2), and centralized pipes (CW 3 in the figures), except the blank system. Removals and transformations of nitrogen and sulfate as well as carbon release in the BSCWs were investigated and comparatively assessed. Results showed that the supplements of flower straws could greatly enhance both the nitrate and sulfate removals, and good performance was achieved during the beginning operation period of 30 days, followed by decline due to insufficient organic carbon supply. Nitrate removal efficiency was significantly higher and more stable compared to sulfate. The highest removal rates of nitrate and sulfate were achieved in the CW 3, with a mean value of 4.33 g NO3--N·m-2 d-1 and 2.74 g SO42--S·m-2 d-1, respectively, although the differences among the experimental microcosms were not statistically significant. However, almost the same TN removal rate (3.40-3.47 g N·m-2 d-1) was obtained due to the productions of NO2--N and NH4+-N and leaching of organic N from the straws. High contents of organic carbon and colored substance were leached from the straws during the initial 10 days, but dropped rapidly to low levels, and could hardly determined after 30 days operation. The post-treatment zone could further eliminate various contaminants, but the capability was limited. Inorganic carbon (IC) concentration was detected to be a highly good indicator for the estimation of nitrate and sulfate removal efficiencies of the BSCWs, particularly for nitrate.

Remediation of nitrate-contaminated wastewater using denitrification biofilters with straws of ornamental flowers added as carbon source.

Straws of four ornamental flowers (carnation, rose, lily, and violet) were added into denitrification biofilters using gravel as matrix through vertically installed perforated polyvinylchloride pipes to provide organic carbon for the treatment of nitrate-contaminated wastewater operating in batch mode. Removal efficiencies of nitrate and phosphate, as well as temporal variations of nitrogen and carbon during batches 10 and 19, were investigated and assessed. Nitrate removal was efficiently enhanced by the addition of flower straws, but decreased gradually as the organic substances were consumed. Phosphate removal was also improved, although this very limited. High nitrate removal rates were achieved during the initial 12 h in the two batches each lasting for 3 days, along with the depletion of influent dissolved oxygen due to aerobic degradation of the organic compounds. NO2(-)-N of 0.01-2.83 mg/L and NH4(+)-N of 0.02-1.69 mg/L were formed and both positively correlated to the nitrate reduced. Inorganic carbon (IC) concentrations increased during the batches and varied conversely with the nitrate contents, and could be indicative of nitrate removal due to the highly significant positive correlation between NO3(-)-N removed and IC concentration (r(2) = 0.881, p < 0.0001). It is feasible and economical to use the denitrification biofilter to treat nitrate-contaminated wastewater, although further optimization of carbon source addition is still required.

Electroacupuncture improves cardiac function and remodeling by inhibition of sympathoexcitation in chronic heart failure rats.

Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.