Endothelium (EC) is a key component of blood–brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood. Here we showed that necroptosis was a mechanism underlying EC death, which promoted BBB breakdown after I/R injury. Treatment of rats with receptor interacting protein kinase 1 (RIPK1)-inhibitor, necrostatin-1 reduced endothelial necroptosis and BBB leakage. We furthermore showed that perivascular M1-like microglia-induced endothelial necroptosis leading to BBB disruption requires tumor necrosis factor-α (TNF-α) secreted by M1 type microglia and its receptor, TNF receptor 1 (TNFR1), on endothelium as the primary mediators of these effects. More importantly, anti-TNFα (infliximab, a potent clinically used drug) treatment significantly ameliorate endothelial necroptosis, BBB destruction and improve stroke outcomes. Our data identify a previously unexplored role for endothelial necroptosis in BBB disruption and suggest infliximab might serve as a potential drug for stroke therapy.

A metal-free, highly regioselective and stereoregular ring-opening alternating copolymerization of monosubstituted epoxides with tricyclic anhydrides was achieved to yield well-defined polyesters.

Abstract:The main components of sambong (Blumea balsamifera) are listed in this article. The whole plant and its crude extracts, as well as its isolated constituents, display numerous biological activities, such as antitumor, hepatoprotective, superoxide radical scavenging, antioxidant, antimicrobial and anti-inflammation, anti-plasmodial, anti-tyrosinase, platelet aggregation, enhancing percutaneous penetration, wound healing, anti-obesity, along with disease and insect resistant activities. Although many experimental and biological studies have been carried out, some traditional uses such as rheumatism healing still need to be verified by scientific pharmacological studies, and further studies including phytochemical standardization and bioactivity authentication would be beneficial.

Electroconvulsive therapy (ECT) is one of the most effective treatments for major depression disorder (MDD). ECT can induce neurogenesis and synaptogenesis in hippocampus, which contains distinct subfields, e.g., the cornu ammonis (CA) subfields, a granule cell layer (GCL), a molecular layer (ML), and the subiculum. It is unclear which subfields are affected by ECT and whether we predict the future treatment response to ECT by using volumetric information of hippocampal subfields at baseline? In this study, 24 patients with severe MDD received the ECT and their structural brain images were acquired with magnetic resonance imaging before and after ECT. A state-of-the-art hippocampal segmentation algorithm from Freesurfer 6.0 was used. We found that ECT induced volume increases in CA subfields, GCL, ML and subiculum. We applied a machine learning algorithm to the hippocampal subfield volumes at baseline and were able to predict the change in depressive symptoms (r = 0.81; within remitters, r = 0.93). Receiver operating characteristic analysis also showed robust prediction of remission with an area under the curve of 0.90. Our findings provide evidence for particular hippocampal subfields having specific roles in the response to ECT. We also provide an analytic approach for generating predictions about clinical outcomes for ECT in MDD.

The mechanism of blood-brain barrier (BBB) disruption, involved in poststroke edema and hemorrhagic transformation, is important but elusive. We investigated microRNA-150 (miR-150)-mediated mechanism in the disruption of BBB after stroke in rats. We found that up-regulation of miR-150 increased permeability of BBB as detected by MRI after permanent middle cerebral artery occlusion in vivo as well as increased permeability of brain microvascular endothelial cells after oxygen-glucose deprivation in vitro. The expression of claudin-5, a key tight junction protein, was decreased in the ischemic boundary zone after up-regulation of miR-150. We found in brain microvascular endothelial cells that overexpression of miR-150 decreased not only cell survival rate but also the expression levels of claudin-5 after oxygen-glucose deprivation. With dual-luciferase assay, we confirmed that miR-150 could directly regulate the angiopoietin receptor Tie-2. Moreover, silencing Tie-2 with lentivirus-delivered small interfering RNA reversed the effect of miR-150 on endothelial permeability, cell survival, and claudin-5 expression. Furthermore, poststroke treatment with antagomir-150, a specific miR-150 antagonist, contributed to BBB protection, infarct volume reduction, and amelioration of neurologic deficits. Collectively, our findings suggested that miR-150 could regulate claudin-5 expression and endothelial cell survival by targeting Tie-2, thus affecting the permeability of BBB after permanent middle cerebral artery occlusion in rats, and that miR-150 might be a potential alternative target for the treatment of stroke.-Fang, Z., He, Q.-W., Li, Q., Chen, X.-L., Baral, S., Jin, H.-J., Zhu, Y.-Y., Li, M., Xia, Y.-P., Mao, L., Hu, B. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats. FASEB J. 30, 2097FASEB J. 30, -2107FASEB J. 30, (2016. www.fasebj.orgIschemic stroke-induced endothelial dysfunction increases microvascular permeability and blood-brain barrier (BBB) leakage, subsequently causing life-threatening cerebral edema and hemorrhagic transformation (1-3). Prevention of BBB disruption is an important therapeutic strategy in stroke management. Recently some pioneer studies have revealed the roles of microRNAs (miRNAs) in maintaining BBB integrity under neuroinflammatory conditions (4, 5). Concerning stroke, although research has been done on the expression of circulating miRNAs (6, 7), the specific function of miRNAs on poststroke BBB disruption is still largely unknown.MicroRNA-150 (miR-150), a miRNA that is well characterized in tumorigenesis and inflammation, was demonstrated to be an epigenetic regulator of endothelial functions (8, 9). The expression of miR-150 is suppressed under hypoxia (10) and significantly down-regulated after ischemic stroke (7). However, whether miR-150 exerts any effect on BBB homeostasis after stroke is unclear. In this study, we found that overexpression of miR-150 after permanent middle cerebral artery occlusio...

Petiole explants were obtained from in vitro grown diploid (2x = 22) Echinacea purpurea plantlets. Shoots were regenerated by culturing the explants on MS basal medium containing 0.3 mg/L benzyladenine (BA), 0.01 mg/L naphthaleneacetic acid (NAA) and four concentrations (30, 60, 120, and 240 mg/L) of colchicine for 30 days, or 120 mg/L of colchicine for various durations (7, 14, 21, and 28 days). The regenerated shoots were induced to root on MS basal medium with 0.01 mg/L NAA, and then the root-tips of the regenerated shoots were sampled for count of chromosome number. It was found that a treatment duration of >7 days was necessary for induction of tetraploid (4x = 44) shoots, and treatment with 120 mg/L colchicine for 28 days was the most efficient for induction of tetraploids, yielding 23.5% of tetraploids among all the regenerated shoots. Chimeras were observed in almost all the treatments. However, the ratio of tetraploid to diploid cells in a chimeric plant was usually low. In comparison with diploid plants, tetraploid plants in vitro had larger stomata and thicker roots with more root branches, and had prominently shorter inflorescence stalk when mature.

Blumea balsamifera, also named Ainaxiang, is widely used as an ancient medicinal herb in tropical and subtropical Asia. It is rich in essential oils. In this work the essential oils of B. balsamifera from different plant organs and in different months were extracted, and then analyzed by gas chromatography-mass spectrometry. The results showed that essential oil yield of young leaves was the highest (0.65 mL/100 g), followed by mature leaves (0.57 mL/100 g), and the oil yield was higher in October (0.47 mL/100 g) than other months. A total of 44 compounds were identified, representing 92.64%-96.71% of the oil. Eighteen common chemical components were found among the six plant organs, representing >80% of the oil constituents. l-borneol was the main ingredient in leaves, and its content was the highest in senescent leaves and in December. In the essential oils of young shoots and young stems, the main component was dimethoxydurene. Antioxidant activity was also determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-carotene bleaching (BCB) assays. The results indicated that the β-carotene bleaching activity was far stronger than the DPPH radical-scavenging capacity, and the young leaves and young shoots showed stronger antioxidant activity. Dimethoxydurene, β-caryophyllene, and α-caryophyllene play a positive role in good antioxidant activity, while β-eudesmol, phytol, and tetradecanal play a negative role. The antioxidant activity revealed in this study might help in developing this promising bioresource for use in the medicinal and cosmetic industries.

One-step chemoselective copolymerization of heterocyclic mixtures has been proved to be an efficient and straightforward approach to sequence-controlled (multi)block copolyesters compared with sequential addition and the macroinitiator method. However, the scope of the monomer substrates is limited to the oxygenated heterocycles, and cyclic monomers containing other heteroatoms are underexplored. In this work, we extended the chemoselective polymerization to sulfurcontaining heterocycles and successfully synthesized sequence-controlled block copolymers polyester-block-poly(ester-alt-thioester)s from anhydride/thioanhydride/epoxide monomers. This is realized via highly selective copolymerization of anhydride/epoxide prior to thioanhydride/epoxide copolymerization using rationally designed aluminum-based catalysts bearing bipyridine bisphenolate ligands. A significant difference between the reactivity of anhydride and thioanhydride with alkoxide chain end led to the excellent chemoselectivity. Moreover, transesterification side reactions are completely inhibited even at a high temperature up to 80 °C during the copolymerization, resulting in block copolymers with well-defined sequence structure on the polymer chains. Chemoselective copolymerization is also highly controlled in the use of a family of different epoxide derivatives, providing a powerful tool box for creating various advanced polythioesters for many different applications.