Potential anticancer activities of securinine and its molecular targets.

BACKGROUND: Securinine is an alkaloid identified from the roots and leaves of the shrub Flueggea suffruticosa (Pall.) Baill. The molecular structure of securinine consists of four rings, including three chiral centers. It has been suggested that securinine can be chemically synthesized from tyrosine and lysine. Securinine has long been used to treat central nervous system diseases. In recent years, more and more evidence shows that securinine also has anticancer activity, which has not been systematically discussed and analyzed. PURPOSE: This study aims to propose an overall framework to describe the molecular targets of securinine in different signal pathways, and discuss the current status and prospects of each pathway, so as to provide a theoretical basis for the development securinine as an effective anticancer drug. METHODS: The research databases on the anticancer activity of securinine from PubMed, Scopus, Web of Science and ScienceDirect to 2021 were systematically searched. This paper follows the Preferred Reporting Items and Meta-Analysis guidelines. RESULTS: Securinine has the ability to kill a variety of human cancer cells, including, leukemia as well as prostate, cervical, breast, lung, and colon cancer cells. It can regulate the signal pathways of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, Wnt and Janus kinase-signal transducer and activator of transcription, promote cancer cell apoptosis and autophagy, and inhibit cancer cell metastasis. Securinine also has the activity of inducing leukemia cell differentiation. CONCLUSION: Although there has been some experimental evidence indicating the anticancer effect of securinine and its possible pharmacology, in order to design more effective anticancer drugs, it is necessary to study the synergy of intracellular signaling pathways. More in vivo experiments and even clinical studies are needed, and the synergy between securinine and other drugs is also worth studying.

A multicentre randomized clinical trial on efficacy and safety of huxin formula in patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is widely used in clinical treatment of coronary artery disease. However, the effects of PCI on preventing restenosis after revascularization and improving the quality of life were not satisfying. Huxin Formula is formulated by modifying an experienced Chinese medicine formula and has been widely used in clinical practice due to its marked effects on coronary heart disease. A multicentre double-blind randomized controlled clinical trial was designed to evaluate the effects and safety of Huxin Formula in patients undergoing PCI. Our results showed that there was no significant difference between the two groups in main outcomes. For patients with ejection fraction (EF) >50%, score of the quality of life scale was higher in treatment group compared with control group. For patients with unstable angina, score of the quality of life scale in 360 days was significantly higher in treatment group compared with control group (P < 0.05). No obvious adverse reaction was found in the use of Huxin Formula. In conclusion, Huxin Formula, believed to be a safe treatment for patients after PCI, has benefits in improving the quality of life in patients with unstable angina though it failed to show superiority in primary and secondary outcomes.

Activated nuclear factor-kappaB and increased tumor necrosis factor-alpha in atrial tissue of atrial fibrillation.

OBJECTIVES: To depict the interaction between atrial fibrillation (AF) and inflammatory reaction, studies were taken to measure the activity of NF-kappaB in myocardium, the concentration of regional inflammatory factors and the pathological process of the right atrium in patients with AF. DESIGN: Patients with valvular disease with AF or sinus rhythm (SR) were recruited and compared. Before the extracorporal circulation, about 250 mg tissue of right atrium was collected for pathological examination. The activity of NF-kappaB in myocardium was measured by electrophoretic mobility shift assay (EMSA), and the concentration of cardiac tissue interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha) was determined by radioimmuoassay. RESULTS: Patients with valvular disease with AF exhibited higher NF-kappaB activity, higher concentration of TNF-alpha and IL-6, severe lymphomonocyte infiltration, and more fibrosis than those patients with valvular disease with SR. There were significant positive correlations among NF-kappaB activity and levels of TNF-alpha and IL-6 and collagen volume fraction. CONCLUSIONS: This study proved the presence of inflammation in atrial myocardium by triggering inflammatory reaction.

Continuous recording of pulmonary artery diastolic pressure and cardiac output using a novel ultrasound transducer.

BACKGROUND: The feasibility of hands-free transthoracic continuous determination of pulmonary artery (PA) diastolic pressure (PAD) and cardiac output (CO) by Doppler ultrasound has not been previously demonstrated. We developed a 2.5-MHz spherical transducer mounted in an external housing to permit steering in 360 degrees (Contison). The external housing was attached to the chest wall using an adhesive patch. METHODS AND RESULTS: Fifty patients in the coronary care department who had PA catheters had Doppler ultrasound studies. The 2.5-MHz spherical transducer was placed at the left sternal border to permit imaging of the pulmonic valve and was attached to a commercial ultrasound machine. The PA was imaged and its diameter measured. The pulmonary flow velocity signal was recorded and the time velocity integral obtained. The CO was calculated as: CO = time velocity integral of the PA systolic flow velocity signal x pi diameter(2) divided by 4 x heart rate. The pulmonary regurgitation signal was then recorded and the end-diastolic velocity of the regurgitant signal was measured. Right atrial pressure was assessed from the jugular venous pressure or from the size and pulsatility of the inferior vena cava. The PADP was calculated as: PADP = 4 end-diastolic velocity of the regurgitant signal(2) + right atrial pressure. The CO, PADP, and pulmonary wedge pressure were recorded from the PA catheter immediately after the ultrasound studies. Serial data were obtained every half hour or 1 hour up to a maximum of 5 hours. Adequate Doppler signals were obtained in 43 patients. RESULTS: There was a good correlation between the PADP by Doppler versus PA catheter (r = 0.90, standard error of the estimate = 3.3 mm Hg); PADP by Doppler versus PA wedge pressure (r = 0.88, standard error of the estimate = 3.7 mm Hg); and CO by Doppler versus PA catheter (r = 0.92, standard error of the estimate = 0.7 L/min). CONCLUSION: The 2.5-MHz spherical transducer permitted accurate assessment of CO and PAD. This transducer could be of potential value in monitoring patients in the intensive care setting.