Alpha-solanine inhibits endothelial inflammation via nuclear factor kappa B signaling pathway.

BACKGROUND: Alpha-solanine (α-solanine) is the main glycoalkaloid in potato plants. It possesses anticarcinogenic properties and exerts toxic effects. Alpha-solanine can regulate the nuclear factor kappa B (NF-κB) signaling pathway in cancer cells and macrophages. However, little is known about the anti-inflammatory effects and the related molecular mechanisms of α-solanine on endothelial cells. OBJECTIVES: This study aims to examine the effects of α-solanine on endothelial inflammation in vitro, and to evaluate its influence on regulating the NF-κB signaling pathway. MATERIAL AND METHODS: Tumor necrosis factor alpha (TNF-α)-pcDNA3.1(+) plasmid vector was constructed and transfected into human umbilical vein endothelial cells (HUVECs). The expression of TNF-α was examined with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Following treatment with α-solanine or the specific NF-κB inhibitor SN50 for 24 h, cell viability was detected using Cell Counting Kit-8 (CCK-8) assay. Interleukin 6 (IL-6) and TNF-α levels in cell supernatant were detected using enzyme-linked immunosorbent assay (ELISA). The relative protein levels of phospho-P65 (p-P65), phospho-inhibitor of NF-κBα (p-IκBα) and IκB kinase (IKK) α/ß were examined with western blot. RESULTS: The α-solanine inhibits TNF-α-induced inflammatory injury in HUVECs. Compared with control cells, the cell viability was significantly decreased, the levels of TNF-α and IL-6 were significantly increased, and the relative protein levels of p-P65, p-IκBα and IKKα/ß were significantly upregulated in TNF-α-overexpressed cells. The treatment with α-solanine or SN50 decreased the levels of TNF-α and IL-6, and downregulated the relative protein levels of p-P65, p-IκBα and IKKα/ß in TNF-α-overexpressed HUVECs. CONCLUSIONS: This study demonstrated for the first time that α-solanine inhibits endothelial inflammation through the NF-κB signaling pathway. The α-solanine was suggested to be an inhibitor of the NF-κB signaling pathway in endothelial cells. The anti-inflammatory effect of α-solanine may provide a new perspective for the prevention and treatment of phlebitis.

[Case-control study on minimally invasive percutaneous plate osteosynthesis for the treatment of distal tibial comminuted fractures at different operation times].

OBJECTIVE: To compare clinical outcomes of minimally invasive percutaneous plate osteosynthesis (MIPPO) in treating distal tibial comminuted fractures at early and delayed stage. METHODS: From January 2006 to January 2012,66 patients with distal tibial comminuted fractures were treated by MIPPO. All patients were divided into primary group and delayed group according to operation time. There were 31 patients in primary group, including 18 males and 13 females aged 21 to 57 years old with an average of (39.0 +/- 17.8), treated by MIPPO at primary stage,according to Tscherne soft tissue injury, 18 cases were grade I ,12 cases were grade II and 1 case were grade III. Thirty-five patients were treated by MIPPO at delayed stage, including 16 males and 19 females aged 24 to 55 years old with an average of (39.5 +/- 15.2), according to Tscherne soft tissue injury, 6 cases were grade I, 26 cases were grade II and 3 cases were grade III. Operation time, blood loss, hospital stay, fracture healing time and complications of two groups were recorded and observed, Lowa scoring of ankle joint were used to evaluated therapeutic effects at final following and AP and lateral X-rays were used to evaluated fracture reduction and alignment. RESULTS: All patients were followed up, the time of following-up of primary group was (13.5 +/- 3.5) months, (15.2 +/- 3.8) months in delayed group, there was no significant meaning between two groups (t = 1.882, P = 0.064). There was no significant differences between two groups in operation time and blood loss (P > 0.05), but hospital stay in primary group was shorter than that of delayed group(P<0.05). There was no significant meaning between primary group (5.5 +/- 2.8) and delayed group (6.2 +/- 3.1) in fracture healing time (t = 0.958, P = 0.342); there was no significant meaning between primary group (87.6 +/- 6.8) and delayed group (89.6 +/- 5.2) in Lowa scores at final following-up (t = 1.351, P = 0.182). Two cases occurred postoperative superficial inflammatory reaction around fibular incision in primary group, 1 case occurred postoperative superficial inflammatory reaction around fibular incision and 1 case occurred delayed deep incision infection in delayed group at four months after operation. There was no significant differences in incidence of postoperative soft tissue complications between primary group (6.5%) and delayed group (5.7%) (t = 0.016, P = 0.900). CONCLUSION: For distal tibial comminuted fractures with grade I and II of Tscherne soft tissue injury, MIPPO at primary stage can not increase incidence of soft tissue complications, also can obtain the same clinical outcomes just like delayed MIPPO.

Overshoot in biological systems modelled by Markov chains: a non-equilibrium dynamic phenomenon.

A number of biological systems can be modelled by Markov chains. Recently, there has been an increasing concern about when biological systems modelled by Markov chains will perform a dynamic phenomenon called overshoot. In this study, the authors found that the steady-state behaviour of the system will have a great effect on the occurrence of overshoot. They showed that overshoot in general cannot occur in systems that will finally approach an equilibrium steady state. They further classified overshoot into two types, named as simple overshoot and oscillating overshoot. They showed that except for extreme cases, oscillating overshoot will occur if the system is far from equilibrium. All these results clearly show that overshoot is a non-equilibrium dynamic phenomenon with energy consumption. In addition, the main result in this study is validated with real experimental data.

Kinetic behavior of the general modifier mechanism of Botts and Morales with non-equilibrium binding.

In this paper, we perform a complete analysis of the kinetic behavior of the general modifier mechanism of Botts and Morales in both equilibrium steady states and non-equilibrium steady states (NESS). Enlightened by the non-equilibrium theory of Markov chains, we introduce the net flux into discussion and acquire an expression of the rate of product formation in NESS, which has clear biophysical significance. Up till now, it is a general belief that being an activator or an inhibitor is an intrinsic property of the modifier. However, we reveal that this traditional point of view is based on the equilibrium assumption. A modifier may no longer be an overall activator or inhibitor when the reaction system is not in equilibrium. Based on the regulation of enzyme activity by the modifier concentration, we classify the kinetic behavior of the modifier into three categories, which are named hyperbolic behavior, bell-shaped behavior, and switching behavior, respectively. We show that the switching phenomenon, in which a modifier may convert between an activator and an inhibitor when the modifier concentration varies, occurs only in NESS. Effects of drugs on the Pgp ATPase activity, where drugs may convert from activators to inhibitors with the increase of the drug concentration, are taken as a typical example to demonstrate the occurrence of the switching phenomenon.