Trifluorobenzamidine prevents allergic rhinitis by regulating IgE, IL-4 and IL-5 in T-cells

Purpose: To investigate the effect of trifluorobenzamidine (TBI) on a mouse model of ovalbumin (OVA)- induced allergic rhinitis. Methods: Allergic rhinitis was established in mice via sensitization on days 1, 5 and 14 through intraperitoneal injection of OVA (100 μg) in PBS. On day 15, the mice were subjected to intranasal exposure to OVA (1.5 mg dissolved in PBS). Prior to 10 days of intranasal exposure to OVA, the micewere treated with TBI at doses of 5, 10 and 20 μg/kg. Cytokine levels were determined using enzymelinked immunosorbent assay (ELISA) kits, while cyclooxygenase (COX)-2 and caspase-1 activity were assayed with western blotting. Results: Treatment with TBI significantly (p < 0.05) reduced OVA-mediated increases in nasal rub scores, and decreased serum levels of IgE, TNF-α, thymic stromal lymphopoietin (TSLP), IL-1β and histamine in mice. It also significantly regulated spleen weight and IL-4 secretion (p < 0.05) in OVAadministered mice. TBI significantly downregulated the expressions of IL-5, IL-13, TNFα, TSLP, IL-1β and IL-6 (p < 0.05). Administration of TBI caused a marked reduction in OVA-mediated increase in caspase-1 activity in mice intranasal tissues, and also significantly reduced OVA-induced excessive production of MIP-2 and ICAM-1 (p < 0.05). Moreover, TBI prevented OVA-induced infiltration of eosinophils and mast cells into intranasal tissues (p < 0.05). Conclusion: TBI reduces levels of IgE and various pro-inflammatory cytokines in OVA-administered mice. It also regulates Th1:Th2 ratio, inhibited activity of caspase-1, suppressed mast cell/eosinophil infiltration and reduced ICAM-1 and MIP-2 levels. Therefore, TBI possesses inhibitory potential against rhinitis allergy, and thus can potentially be developed as a new treatment strategy for asthma. Keywords: Trifluorobenzamidine, Anti-inflammation, Allergic rhinitis, Cytokines, Caspase-1, Itchin

Stabilized Wide Bandgap MAPbBr\u3csub\u3ex\u3c/sub\u3eI\u3csub\u3e3– x\u3c/sub\u3e Perovskite by Enhanced Grain Size and Improved Crystallinity

Methylammonium lead trihalide perovskite (MAPbX3, where MA is methylammonium, and X is a halide)-based solar cells have been intensively investigated recently, with the demonstrated certified solar power conversion efficiency (PCE) exceeding 20%. To further boost the PCE to beyond the Schockley–Queisser limit, tandem structured solar cells have been investigated based on integrating MAPbX3 and low bandgap solar cells. However, the efficiency of the two-terminal integrated perovskite-silicon tandem cells is still low. The best reported efficiency of 13.7% for this type of tandem cells is far smaller than the individual cells yet, partially due to the limited performance of the mixed-halide perovskite MAPbBrxI 3– x solar cell employed in this structure. The mixed-halide perovskite MAPbBrx I3– x is still one of the most promising candidates as the wide-bandgap light absorber for the tandem application to match the bandgap of silicon, considering its continuously tunable bandgap from 1.6 eV to 2.3 eV with different bromide incorporation ratio. However, the application of MAPb-Brx I3– x based solar cells has been reported to confront with one big challenge of intrinsic light instability. The MAPbBrx I3– x materials on mesoporous scaffold were shown to be unstable under illumination with a photo-excited phase-separation into two phases, one iodine-rich phase and one iodine-poor phase. The lower bandgap phase thus acts as the charge traps, which was hypothesized to be responsible to the severely reduced device open circuit voltage and device PCE for the mixed-halide perovskite devices

In vitro evaluation of marine-microorganism extracts for anti-viral activity

Viral-induced infectious diseases represent a major health threat and their control remains an unachieved goal, due in part to the limited availability of effective anti-viral drugs and measures. The use of natural products in drug manufacturing is an ancient and well-established practice. Marine organisms are known producers of pharmacological and anti-viral agents. In this study, a total of 20 extracts from marine microorganisms were evaluated for their antiviral activity. These extracts were tested against two mammalian viruses, herpes simplex virus (HSV-1) and vesicular stomatitis virus (VSV), using Vero cells as the cell culture system, and two marine virus counterparts, channel catfish virus (CCV) and snakehead rhabdovirus (SHRV), in their respective cell cultures (CCO and EPC). Evaluation of these extracts demonstrated that some possess antiviral potential. In sum, extracts 162M(4), 258M(1), 298M(4), 313(2), 331M(2), 367M(1) and 397(1) appear to be effective broad-spectrum antivirals with potential uses as prophylactic agents to prevent infection, as evident by their highly inhibitive effects against both virus types. Extract 313(2) shows the most potential in that it showed significantly high inhibition across all tested viruses. The samples tested in this study were crude extracts; therefore the development of antiviral application of the few potential extracts is dependent on future studies focused on the isolation of the active elements contained in these extracts

Silica nanoparticles enhance autophagic activity, disturb endothelial cell homeostasis and impair angiogenesis

BACKGROUND: Given that the effects of ultrafine fractions (<0.1 μm) on ischemic heart diseases (IHD) and other cardiovascular diseases are gaining attention, this study is aimed to explore the influence of silica nanoparticles (SiNPs)-induced autophagy on endothelial cell homeostasis and angiogenesis. METHODS AND RESULTS: Ultrastructural changes of autophagy were observed in both vascular endothelial cells and pericytes in the heart of ICR mice by TEM. Autophagic activity and impaired angiogenesis were further confirmed by the immunohistochemistry staining of LC3 and VEGFR2. In addition, the immunohistochemistry results showed that SiNPs had an inhibitory effect on ICAM-1 and VCAM-1, but no obvious effect on E-selectin in vivo. The disruption of F-actin cytoskeleton occurred as an initial event in SiNPs-treated endothelial cells. The depolarized mitochondria, autophagic vacuole accumulation, LC3-I/LC3-II conversion, and the down-regulation of cellular adhesion molecule expression were all involved in the disruption of endothelial cell homeostasis in vitro. Western blot analysis indicated that the VEGFR2/PI3K/Akt/mTOR and VEGFR2/MAPK/Erk1/2/mTOR signaling pathway was involved in the cardiovascular toxicity triggered by SiNPs. Moreover, there was a crosstalk between the VEGFR2-mediated autophagy signaling and angiogenesis signaling pathways. CONCLUSIONS: In summary, the results demonstrate that SiNPs induce autophagic activity in endothelial cells and pericytes, subsequently disturb the endothelial cell homeostasis and impair angiogenesis. The VEGFR2-mediated autophagy pathway may play a critical role in maintaining endothelium and vascular homeostasis. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by nano-sized particles. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-014-0050-8) contains supplementary material, which is available to authorized users

Solution-Processed Nanoparticle Super-Float-Gated Organic Field-Effect Transistor as Un-cooled Ultraviolet and Infrared Photon Counter

High sensitivity photodetectors in ultraviolet (UV) and infrared (IR) range have broad civilian and military applications. Here we report on an un-cooled solution-processed UV-IR photon counter based on modified organic field-effect transistors. This type of UV detectors have light absorbing zinc oxide nanoparticles (NPs) sandwiched between two gate dielectric layers as a floating gate. The photon-generated charges on the floating gate cause high resistance regions in the transistor channel and tune the source-drain output current. This ‘‘super-float-gating’’ mechanism enables very high sensitivity photodetectors with a minimum detectable ultraviolet light intensity of 2.6 photons/µm2s at room temperature as well as photon counting capability. Based on same mechansim, infrared photodetectors with lead sulfide NPs as light absorbing materials have also been demonstrated

Solution-Processed Nanoparticle Super-Float-Gated Organic Field-Effect Transistor as Un-cooled Ultraviolet and Infrared Photon Counter

High sensitivity photodetectors in ultraviolet (UV) and infrared (IR) range have broad civilian and military applications. Here we report on an un-cooled solution-processed UV-IR photon counter based on modified organic field-effect transistors. This type of UV detectors have light absorbing zinc oxide nanoparticles (NPs) sandwiched between two gate dielectric layers as a floating gate. The photon-generated charges on the floating gate cause high resistance regions in the transistor channel and tune the source-drain output current. This ‘‘super-float-gating’’ mechanism enables very high sensitivity photodetectors with a minimum detectable ultraviolet light intensity of 2.6 photons/µm2s at room temperature as well as photon counting capability. Based on same mechansim, infrared photodetectors with lead sulfide NPs as light absorbing materials have also been demonstrated

Twist1 Controls Lung Vascular Permeability and Endotoxin-Induced Pulmonary Edema by Altering Tie2 Expression

Tight regulation of vascular permeability is necessary for normal development and deregulated vascular barrier function contributes to the pathogenesis of various diseases, including acute respiratory distress syndrome, cancer and inflammation. The angiopoietin (Ang)-Tie2 pathway is known to control vascular permeability. However, the mechanism by which the expression of Tie2 is regulated to control vascular permeability has not been fully elucidated. Here we show that transcription factor Twist1 modulates pulmonary vascular leakage by altering the expression of Tie2 in a context-dependent way. Twist1 knockdown in cultured human lung microvascular endothelial cells decreases Tie2 expression and phosphorylation and increases RhoA activity, which disrupts cell-cell junctional integrity and increases vascular permeability in vitro. In physiological conditions, where Ang1 is dominant, pulmonary vascular permeability is elevated in the Tie2-specific Twist1 knockout mice. However, depletion of Twist1 and resultant suppression of Tie2 expression prevent increase in vascular permeability in an endotoxin-induced lung injury model, where the balance of Angs shifts toward Ang2. These results suggest that Twist1-Tie2-Angs signaling is important for controlling vascular permeability and modulation of this mechanism may lead to the development of new therapeutic approaches for pulmonary edema and other diseases caused by abnormal vascular permeability