Mechanism of action of Sambucus williamsii Hance var. miquelii in the treatment of osteoporosis analyzed by UHPLC-HRMS/MS combined network pharmacology and experimental validation.

Sambucus williamsii Hance var. miquelii(SWH) is a precious wild Chinese herb whose fruit, rhizome, leaves and root bark can be used as medicine. Sambucus Linn has pharmacological effects such as anti-osteoporosis, promoting fracture healing, anti-viral and anti-inflammatory. In this study, the main chemical components of the alcoholic extracts from SWH were rapidly identified by ultra-high performance liquid chromatography-quadrupole orbit trap high-resolution mass spectrometry (UHPLC- HRMS MS), and a total of 42 compounds were characterized from the alcoholic extracts of SWH. The results of network pharmacological validation showed that kaempferol, quercetin, luteolin, isorhamnetin and morroniside were the main active components, and KEGG enrichment demonstrated that SWH mainly affected the signaling pathways such as PI3K-Akt, TNF and FoxO by modulating the related targets such as AKT1, PIK3R1, EGFR, RELA SRC and PTGS2. The molecular docking results showed binding solid activity between the main active components of SWH and the targets. The network pharmacology was validated by establishing an animal model of osteoporosis (OP) in rats by gavage administration of vitamin A acid. The results of the pharmacological experiments showed that SWH could improve the degree of bone loss in the femur of osteoporotic rats, increase the number of trabeculae and decrease trabeculae porosity, up-regulate the Ca and P content in the serum of OP rats, down-regulate the scope of ALP and BGP in the serum, and promote the calcification of the bone matrix, and then exert the anti-OP efficacy. In this study, network pharmacology and pharmacological experiments verified the pharmacological mechanism of SWH in anti-OP rats. This provides a theoretical basis for the research and development of anti-OP drugs and a reference for the application of other traditional Chinese medicines in treating OP diseases.

Study on the technology of efficient extraction of eleutheroside E from Acanthopanax senticosus by green solvent DES.

OBJECTIVES: Acanthopanax senticosus (Rupr. & Maxim.) Harms is a medicinal and edible plant which is clinically used for the recovery and treatment of cardiovascular and central diseases. As a characteristic active pharmaceutical ingredient of Acanthopanax senticosus, eleutheroside E is the core of the therapeutic effect. Organic solvent extraction has low selectivity, low extraction rate, difficulty in separation and purification and safety risks. The purpose of this study was to extract the effective component of Acanthopanax senticosus with a new green solvent. METHODS: In this article, two kinds of deep eutectic solvents (DESs) (DES-1 and DES-2) were synthesised by heating and stirring methods. Eleutheroside E was extracted by ultrasonic extraction with two kinds of DES as extractants and quantitatively analysed by Orbitrap-tandem mass spectrometry (MS/MS). RESULTS: The main results showed that the initial polarity of the DES was similar to that of 60 to 80% ethanol and hydrogen bond donors were the main factors affecting the polarity of DES. In the test, the viscosity of DES was higher than that of ethanol, and even the addition of a small amount of water (10%) caused intermolecular hydrogen bond disruption and redistribution of the solvent, resulting in a significant decrease in solvent viscosity. The solvents in the test group were stable after standing at 5°C in the dark for 100 days. The extraction rate of eleutheroside E by DES solvent was 5-6 times higher than that by ethanol. DES-1 and DES-2 can efficiently extract eleutheroside E. CONCLUSION: This study developed a new method for the application of the green extraction of eleutheroside E with certain practical significance.

Multi-Task Offloading Based on Optimal Stopping Theory in Edge Computing Empowered Internet of Vehicles.

Vehicular edge computing is a new computing paradigm. By introducing edge computing into the Internet of Vehicles (IoV), service providers are able to serve users with low-latency services, as edge computing deploys resources (e.g., computation, storage, and bandwidth) at the side close to the IoV users. When mobile nodes are moving and generating structured tasks, they can connect with the roadside units (RSUs) and then choose a proper time and several suitable Mobile Edge Computing (MEC) servers to offload the tasks. However, how to offload tasks in sequence efficiently is challenging. In response to this problem, in this paper, we propose a time-optimized, multi-task-offloading model adopting the principles of Optimal Stopping Theory (OST) with the objective of maximizing the probability of offloading to the optimal servers. When the server utilization is close to uniformly distributed, we propose another OST-based model with the objective of minimizing the total offloading delay. The proposed models are experimentally compared and evaluated with related OST models using simulated data sets and real data sets, and sensitivity analysis is performed. The results show that the proposed offloading models can be efficiently implemented in the mobile nodes and significantly reduce the total expected processing time of the tasks.

Influence of Monocalcium Phosphate on the Properties of Bioactive Magnesium Phosphate Bone Cement for Bone Regeneration.

Bone defects occurring for various reasons can lead to deformities and dysfunctions of the human body. Considering the need for clinical applications, it is essential for bone regeneration to exploit a scaffold with bioactive bone cement. In this study, we fabricated bioactive magnesium phosphate bone cement (BMPC) at room temperature; then, it was set at to °C and 100% humidity for 2 h. The process was as follows: Simulating a clinical environment, magnesium oxide (MgO) was formed by calcining basic magnesium carbonate (Mg2(OH)2CO3). MgO, potassium dihydrogen phosphate (KH2PO4) and carboxymethyl chitosan (C20H37N3O14, CMC) were mixed to form magnesium phosphate bone cement (MPC); then, monocalcium phosphate (Ca(H2PO4)2) was added to neutralize the alkaline product after MPC hydration to fabricate bioactive magnesium phosphate bone cement (BMPC). The influence of the doped content of Ca(H2PO4)2 on the properties of bone cement was discussed. The results showed that Ca(H2PO4)2 and CMC can adjust the setting time of bone cement to between 8 and 25 min. The compressive strength increased first and then decreased. After 48 h without additional pressure, the compressive strength reached the maximum value, which was about 38.6 MPa. Ca(H2PO4)2 and CMC can play a synergistic role in regulating the properties of BMPC. The BMPC was degradable in the simulated body fluid (SBF). The results of the cytotoxicity experiment and laser confocal microscopy experiment indicated that BMPC fabricated at room temperature had better biocompatibility and degradability, which was more consistent with clinical operation requirements. BMPC is a promising orthopedic material and is suitable for repairing bone defects.

[Systematic review and sequential analysis of Tanshinone â ¡_A Sodium Sulfonate Injection combined with enalapril in treatment of acute exacerbation of pulmonary heart disease].

To systematically evaluate the clinical efficacy and safety of Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril in the treatment of patients with acute exacerbation of pulmonary heart disease. The randomized controlled trial(RCT) on Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril for acute exacerbation of pulmonary heart disease was screened from EMbase, PubMed, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang from inception to March 20, 2022. Meta-analysis of each index was performed in RevMan 5.3 and TSA 0.9. Finally, 41 RCTs involving 3 865 patients were included. Meta-analysis showed that the observation group had higher total response rate(RR=1.21, 95%CI[1.18, 1.24], P<0.000 01), lower plasma viscosity(MD=-0.25, 95%CI[-0.34,-0.16], P<0.000 01), lower whole blood viscosity(MD=-0.99, 95%CI[-1.14,-0.85], P<0.000 01), and lower hematokrit(MD=-9.03, 95%CI[-10.57,-7.50], P<0.000 01) than the control group. The incidence of adverse effects showed no significant difference between groups(RR=1.42, 95%CI[0.82, 2.45], P=0.21). Sequential analysis showed that Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril exerted definite efficacy in the treatment of acute exacerbation of pulmonary heart disease, and the possibility of false positives was excluded. Based on the existing evidence, Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril can improve the total response rate and reduce plasma viscosity, whole blood viscosity, and hematocrit, demonstrating good safety in patients with acute exacerbation of pulmonary heart disease. In the future, more RCT with large sample size, rigorous design, and in accordance with international norms are needed to further validate the results.

Fabrication and Microstructure of ZnO/HA Composite with In Situ Formation of Second-Phase ZnO.

Nanometer hydroxyapatite (n-HA) powders were synthesized by the chemical precipitation method, and a novel ZnO/HA composite, which consisted of second-phase particles with different sizes and distributions, was successfully fabricated. ZnO/HA composites were prepared by using powder sintering with different Zn contents and a prefabrication pressure of 150 MPa. Microstructure and local chemical composition were analyzed by a scanning electron microscope (SEM) and energy-dispersive spectrometer (EDS), respectively. The phase composition and distribution of the composite were determined with electron back-scattered diffraction (EBSD) and an X-ray diffractometer (XRD), respectively. The experimental results of the XRD showed that the chemical precipitation method was a simple and efficient method to obtain high-purity n-HA powders. When the sintering temperature was lower than 1250 °C, the thermal stability of HA was not affected by the Zn in the sintering process. Due to sintering in an air atmosphere, the oxidation reaction of Zn took place in three stages, and ZnO as the second phase had two different sizes and distributions in the composites. The compressive strength of ZnO/HA composites, of which the highest was up to 332 MPa when the Zn content was 20%, was significantly improved compared with pure HA. The improvement in mechanical properties was mainly due to the distribution of fine ZnO particles among HA grains, which hindered the HA grain boundary migration and refinement of HA grains. As grain refinement increased the area of the grain boundary inside the material, both the grain boundary and second phase hindered crack development in different ways.

A preclinical randomized controlled study of ischemia treated with Ginkgo biloba extracts: Are complex components beneficial for treating acute stroke?

The rigorous design of preclinical experimental studies of candidate neuroprotectants for the treatment of acute ischemic stroke is crucial for the success of subsequent randomized clinical trials. The efficacy of Ginkgo biloba extracts (GBEs) in complex mixtures for the treatment of acute ischemic stroke remains unclear. In this preclinical randomized controlled trail (pRCT), the effects of a novel (n)GBE containing pinitol versus traditional (t)GBE without pinitol were evaluated on the mouse models of acute transient and permanent stroke, separately. The sample size, an important aspect of study design, was calculated based on our experimental data. Mice with ischemia that were induced by transient middle cerebral artery occlusion (tMCAO) or permanent distal middle cerebral artery occlusion (pdMCAO), were treated with vehicle, nGBE, tGBE, or pinitol alone by tail-vein injection. Our results showed that nGBE significantly reduced infarct size in mice with tMCAO compared with vehicle-treated control mice. Both nGBE and tGBE significantly reduced infarct size in mice with pdMCAO compared with the vehicle-treated controls. None of the three treatments rescued weight loss or prevented the neurological deficits in either the tMCAO- or pdMCAO-model mice. These findings suggest that nGBE, which includes all of the components of tGBE and pinitol, is neuroprotective in two ischemic stroke models. Additional studies of complex GBE mixtures for stroke treatment compared to single component medications are undergoing evaluation.