Poly (Betulinic Acid) Nanoparticles Loaded with bFGF Improve Functional Recovery After Spinal Cord Injury.

Oxidative stress (OS) is one of the crucial molecular events of secondary spinal cord injury (SCI). Basic fibroblast growth factor (bFGF) is a multipotent cell growth factor with an anti-oxidant effect. However, bFGF has a short half-life in vivo, which limits its therapeutic application. Biodegradable polymers with excellent biocompatibility have been recently applied in SCI. The negative aspect is that polymers cannot provide a significant therapeutic effect. Betulinic acid (BA), a natural anti-inflammatory compound, has been polymerized into poly (betulinic acid) (PBA) to serve as a drug carrier for bFGF. This study explores the therapeutic effects and underlying molecular mechanisms of PBA nanoparticles (NPs) loaded with bFGF (PBA-bFGF NPs) in SCI. Results show that PBA-bFGF NPs produce remarkable biocompatibility in vivo and in vitro. The results also demonstrate that local delivery of PBA-bFGF NPs enhances motor function recovery, inhibits OS, mitigates neuroinflammation, and alleviates neuronal apoptosis following SCI. Furthermore, the results indicate that local delivery of PBA-bFGF NPs activates the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway following SCI. In summary, results suggest that local delivery of PBA-bFGF NPs delivers potential therapeutic advantages in the treatment and management of SCI.

Over-activation of TRPM2 ion channel accelerates blood-spinal cord barrier destruction in diabetes combined with spinal cord injury rat.

Spinal cord injury (SCI) is a devastating neurological disorder that often results in loss of motor and sensory function. Diabetes facilitates the blood-spinal cord barrier (BSCB) destruction and aggravates SCI recovery. However, the molecular mechanism underlying it is still unclear. Our study has focused on transient receptor potential melastatin 2 (TRPM2) channel and investigated its regulatory role on integrity and function of BSCB in diabetes combined with SCI rat. We have confirmed that diabetes is obviously not conductive to SCI recovery through accelerates BSCB destruction. Endothelial cells (ECs) are the important component of BSCB. It was observed that diabetes significantly worsens mitochondrial dysfunction and triggers excessive apoptosis of ECs in spinal cord from SCI rat. Moreover, diabetes impeded neovascularization in spinal cord from SCI rat with decreases of VEGF and ANG1. TRPM2 acts as a cellular sensor of ROS. Our mechanistic studies showed that diabetes significantly induces elevated ROS level to activate TRPM2 ion channel of ECs. Then, TRPM2 channel mediated the Ca2+ influx and subsequently activated p-CaMKII/eNOS pathway, and which in turn triggered the ROS production. Consequently, over-activation of TRPM2 ion channel results in excessive apoptosis and weaker angiogenesis during SCI recovery. Inhibition of TRPM2 with 2-Aminoethyl diphenylborinate (2-APB) or TRPM2 siRNA will ameliorate the apoptosis of ECs and promote angiogenesis, subsequently enhance BSCB integrity and improve the locomotor function recovery of diabetes combined with SCI rat. In conclusion, TRPM2 channel may be a key target for the treatment of diabetes combined with SCI rat.

Influences of environment, human activity, and climate on the invasion of Ageratina adenophora (Spreng.) in Southwest China.

With economic and social globalization, invasive alien species have significantly threatened local ecological security. Identifying the invasive mechanisms of invasive alien species can aid in preventing species invasions and protecting local ecological and economic security. As a globally invasive plant, Ageratina adenophora (Asteraceae) has spread to many parts of the world and had a seriously impacted the ecology and economy of its invaded areas. Using observational data and Landsat OLI images in an arid valley region in southwest China, this study examined how climate, human activity and environmental factors influence the invasion of A. adenophora and its underlying mechanism. Our results showed that the invasion abundance of A. adenophora was significantly affected by environmental factors (the relative importance was 87.2%), but was less influenced by human activity and climate factors (the relative importance was 2% and 10.8%, respectively). The A. adenophora abundance significantly decreased with aspect, community canopy density, shrub layer coverage, herb layer coverage, Simpson diversity index of shrub and herb layers, the shortest distance to residential areas and temperature seasonality, whereas it increased with soil moisture, temperature annual range, precipitation of wettest month and precipitation of driest month. We conclude that biotic competition is the most influential factor in the invasion of this plant in the arid valley regions. Our results are of great significance for invasion prevention and forest conservation and management in southwest China. Our work emphasized that optimizing the community structure, such as by increasing canopy and shrub coverage and species biodiversity, may help control and mitigate the A. adenophora invasion in southwest China.