A new look at angiogenesis inhibition of geniposide in experimental arthritis by blocking angiopoietin-2 exocytosis.

Angiogenesis is a key player in the pathogenesis of rheumatoid arthritis. Exocytosis from Weibel-Palade bodies is a prerequisite for angiopoietin-2 (Ang-2) to activate endothelial cells and initiate angiogenesis. Geniposide (GE) was previously reported to exert anti-angiogenic effects. The aim of this study was to shed light on whether and how GE regulates Ang-2 exocytosis. A rat model of adjuvant arthritis (AA) was established to evaluate the therapeutic effect of GE (60 and 120 mg/kg) especially in synovial angiogenesis. In addition, the Matrigel plug assay was used to detect the effect of GE (120 and 240 mg/kg) on angiogenesis in AA mice. In vitro, sphingosine-1-phosphate (S1P)-stimulated human umbilical vein endothelial cells (HUVECs) were used to investigate the effect and mechanism of GE on Ang-2 exocytosis. It was found that GE improved the symptoms of AA rats and inhibited angiogenesis in AA, which may be related to the down-regulation of S1P receptors 1, 3 (S1PR1, S1PR3), phospholipase Cß3 (PLCß3), inositol 1,4,5-trisphosphate receptor (IP3 R) and Ang-2 expression. The results of in vitro experiments showed that S1P induced rapid release of Ang-2 from HUVECs with multigranular exocytosis. Suppression of the S1P/S1PR1/3/PLCß3/Ca2+ signal axis by the S1PR1/3 inhibitor VPC23019 and the IP3 R inhibitor 2-APB blocked Ang-2 exocytosis, accompanied by diminished angiogenesis in vitro. GE dose-dependently weakened S1P/S1PR1/3/PLCß3/Ca2+ signal axis activation, Ang-2 exocytosis and angiogenesis in HUVECs (p < 0.05, p < 0.01). Overall, these findings revealed that angiogenesis inhibition of GE was partly attributed to the intervention of Ang-2 exocytosis through negatively modulating the S1P/S1PR1/3/PLCß3/Ca2+ signal axis, providing a novel strategy for rheumatoid arthritis anti-angiogenic therapy.

Comparison Between Percutaneous Kyphoplasty and Percutaneous Vertebroplasty in Terms of Efficacy in Osteoporotic Vertebral Compression Fractures: A Meta-analysis.

Background and Aim: Osteoporotic vertebral compression fractures (OVCFs) are acknowledged to be common fractures, especially in the elderly population. Minimally invasive percutaneous methods of treatment for these fractures such as kyphoplasty (KP) and vertebroplasty (VP) have been valid and effective tools for decreasing clinical problems, which are associated with more beneficial effects compared with traditional methods such as open surgery or conservative treatment. Hence, we conducted the current meta-analysis in order to gather updated evidence for the systematic assessment of clinical and radiographic outcomes of KP compared with VP. Methods: We searched articles published based on the electronic databases, including PubMed, EMBASE, and Cochrane Library. Publications of studies comparing KP with VP in the treatment of OVCFs were collected. After rigorous and thorough review of study quality, we extracted the data on the basis of eligible trials, which analyzed the summary hazard ratios (HRs) of the end points of interest. Results: Our inclusion criteria involved a total of 6 studies. In total, data from 644 patients, 330 who received VP and 284 who received KP, were included in the review. There was no significant difference in either group in terms of visual analog scale (VAS) scores (MD = 0.17; 95% CI, -0.39 to 0.73; P = .56), risk of cement leakage (odds ratio [OR] = 1.31; 95% CI, 0.62 to 2.74; P = .47) or Oswestry Disability Index (ODI) scores (MD = 0.51; 95% CI, -1.87 to 2.88; P = .68). Nevertheless, the injected cement volume (MD = -0.52; 95% CI, -0.88 to -0.15; P = .005) in the VP group was linked to a markedly lower statistically significant trend compared with the KP group. Conclusion: This meta-analysis evaluated acceptable efficacy levels across the involved trials. VP injected cement volume had several advantages in this meta-analysis. Yet, no significant differences were observed in terms of VAS scores, ODI scores, or cement leakage when KP was compared to VP therapy. Given the combined results of our study, the optimal treatment for patients with OVCFs should be determined by further high-quality multicenter randomized controlled trials with longer follow-up and larger sample sizes.

The Integrated Study on the Chemical Profiling to Explore the Constituents and Mechanism of Traditional Chinese Medicine Preparation Huatuo Jiuxin Pills Based on UPLC-Q-TOF/MSE and Network Pharmacology.

Huatuo Jiuxin Pills (HJP), a traditional Chinese medicine (TCM) preparation, has been widely used to treat Cardiovascular Diseases (CVDs) for more than 20 years. However, there were still gaps in the study of chemical components and potential pharmacological effects in the HJP. In this study, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE) combined with network pharmacology was used to comprehensively explore the chemical components in HJP and explore its potential active compounds and the mechanism for the treatment of CVDs. A total of 117 compounds, mainly including saponins, cholic acids, and bufadienolides, were rapidly identified and characterized. Simultaneously, the fragmentation mode and characteristic ion analysis of different types of representative compounds were carried out. Network pharmacology results showed that the more important active ingredients mainly include 5ß-hydroxybufotalin, 19 oxo-cinobufagin, bufarenogin, etc. While, the main targets were PIK3CA, MAPK1, VEGFA and so on. Importantly, HJP has therapeutic effects on CVDs by acting on endocrine resistance, PI3K-Akt signaling pathway, HIF-1 signaling pathway, etc. In addition, molecular docking results showed that the core active ingredients with higher degrees in HJP have a strong affinity with the core targets of CVDs. The current work fills the gap in the chemical substance basis of HJP, and also facilitates a better understanding of the effective components, therapeutic targets, and signaling pathways of HJP in the treatment of CVDs.

The difference of origin and extraction method significantly affects the intrinsic quality of licorice: A new method for quality evaluation of homologous materials of medicine and food.

As a homologous material of both medicine and food, licorice is a famous traditional Chinese medicine. In the application process, different origins and different extraction methods have an impact on the intrinsic quality of licorice. In order to ensure the intrinsic quality of commercially available licorice products, and to explore the influence of origin and extraction methods on the quality of licorice, we put forward a simple and effective discriminatory method for "chemometrics analysis-based fingerprint establishment". First, fingerprints of licorice ethanol extraction (LEE) and licorice water extraction (LWE) were established. Then, similarity analysis (SA), hierarchical clustering analysis (HCA), principal component analysis (PCA) and other chemometrics methods were used to select qualitative and quantitative markers. Besides, the quantitative determination of 7 compounds of licorice with statistical significance was carried out, which provided accurate and informative data for quality evaluation. Finally, discriminant analysis was used to trace the origin of licorice.