Mitochondrial Uncouplers Confer Protection by Activating AMP-Activated Protein Kinase to Inhibit Neuroinflammation Following Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a disease with high disability and mortality rates. Currently, the efficacy of therapies available for ICH is limited. Microglia-mediated neuroinflammation substantially exacerbates brain damage following ICH. Here, we investigated whether mitochondrial uncouplers conferred protection by suppressing neuroinflammation following ICH. To mimic ICH-induced neuroinflammation in vitro, we treated microglia with red blood cell (RBC) lysate. RBC lysate enhanced the expression of pro-inflammatory cytokines in microglia. A clinically used uncoupler, niclosamide (Nic), reduced the RBC lysate-induced expression of pro-inflammatory cytokines in microglia. Moreover, Nic ameliorated brain edema, decreased neuroinflammation, and improved neurological deficits in a well-established mouse model of ICH. Like niclosamide, the structurally unrelated uncoupler carbonyl cyanide p-triflouromethoxyphenylhydrazone (FCCP) reduced brain edema, decreased neuroinflammation, and improved neurological deficits following ICH. It has been reported that mitochondrial uncouplers activate AMP-activated protein kinase (AMPK). Mechanistically, Nic enhanced AMPK activation following ICH, and AMPK knockdown abolished the beneficial effects of Nic following ICH. In conclusion, mitochondrial uncouplers conferred protection by activating AMPK to inhibit microglial neuroinflammation following ICH.

Applying minimal RNA-seq of peripheral blood platelet mRNA to reveal novel biomarkers in male patients with cerebral stroke.

Cerebral stroke is caused by the reduction or disruption of the blood supply to the brain, which results in cell death. Currently, the diagnosis of stroke is troublesome and expensive. In this study, samples of peripheral blood from eight male stroke patients and four male healthy controls were collected. RNA-seq of platelets was performed to detect the differential expression of mRNA in platelets isolated from the samples. Totally, 1091 (429 up-regulated and 662 down-regulated) differentially expressed genes were identified in patients with stroke compared with healthy controls. Analyses based on Gene Ontology and the KEGG pathway revealed that most annotated genes were involved in graft-versus-host disease, cell adhesion molecules signaling pathways, inflammation-related pathways, and so on. RNA expression levels of 15 inflammation-related genes were analyzed using qRT-PCR, especially egr2, which acts as a protector against stroke. In brief, RNA-seq analysis of platelets from all the samples indicated novel candidate genes and pathways that had the potential to be applied to clinical molecular diagnosis of stroke. Besides, this study provided insights into the function and underlying mechanism of stroke.

Near-infrared mediated chemo/photodynamic synergistic therapy with DOX-UCNPs@mSiO2/TiO2-TC nanocomposite.

To integrate photodynamic therapy (PDT) with chemotherapy for enhanced anticancer efficiency, near infrared (NIR) light mediated upconversion nanoparticles@mesoporous silica (UCNPs@mSiO2) nanovehicle was constructed as the nanocarrier. Based on the novel ultraviolet (UV) emission, TiO2 (3.0-3.2eV) was adopted as the photosensitiver (PS) on account of the high activity and excellent stability. Here, a simple host-assembly method was exploited to graft it onto the inner and outer surface of the mSiO2 shell. On the other hand, a UV cleavable o-nitrobenzyl derivative linker (TC linker) was prepared as "gate" to encapsulate anticancer agent doxorubicin (DOX) inside mSiO2, insuring the few prematurity. Under NIR irradiation, the UV emission can excite TiO2 to produce reactive oxygen species (ROS) and also can induce the photodegradation of TC linker and drug release as well. The detailed release kinetics was studied to reveal that it is TC linker to manipulate the NIR-sensitive drug release and the amount of TC linker also can be used to adjust the release performance. The synergistic action of PDT and chemotherapy displays the improved cytotoxicity of DOX-UCNPs@mSiO2/TiO2-TC to HeLa cells under NIR irradiation that makes the potential application in anticancer field due to the superior to any single means.

Synthesis and evaluation of a C8 stationary phase on a silica hydride surface by hydrosilation of 1-octyne.

The silanization/hydrosilation method is used to bond an alkyne (1-octyne) to a silica hydride surface. The new bonded material is characterized by elemental analysis and diffuse reflectance infrared Fourier transform spectroscopy. The hydrophobic behavior of this material was determined by the retention characteristics of aromatic solutes and the shape selectivity as well as phase classification (monomeric or polymeric) was measured by the polycyclic aromatic hydrocarbon mixture standard reference material 869. The presence of residual silanols on the bonded phase was probed by several basic solutes at pH 7. Long-term stability studies were conducted by measuring retention and peak symmetry of basic compounds over several thousand column volumes at pH 10.