Aims: The potential receptor for hydrogen sulfide (H 2 S) remains unknown. Results: H 2 S could directly activate vascular endothelial growth factor receptor 2 (VEGFR2) and that a small interfering RNA (siRNA)-mediated knockdown of VEGFR2 inhibited H 2 S-induced migration of human vascular endothelial cells. H 2 S promoted angiogenesis in Matrigel plug assay in mice and this effect was attenuated by a VEGF receptor inhibitor. Using tandem mass spectrometry (MS), we identified a new disulfide complex located between Cys1045 and Cys1024 within VEGFR2 that was labile to H 2 S-mediated modification. Kinase activity of the mutant VEGFR2 (C1045A) devoid of the Cys1045-Cys1024 disulfide bond was significantly higher than wild-type VEGFR2. Transfection with vectors expressing VEGFR2 (C1045A) caused a significant increase in cell migration, while the migrationpromoting effect of H 2 S disappeared in the cells transfected with VEGFR2 (C1045A). Therefore, the Cys1045-Cys1024 disulfide bond serves as an intrinsic inhibitory motif and functions as a molecular switch for H 2 S. The formation of the Cys1045-Cys1024 disulfide bond disrupted the integrity of the active conformation of VEGFR2. Breaking the Cys1045-Cys1024 disulfide bond recovered the active conformation of VEGFR2. This motif was prone to a nucleophilic attack by H 2 S via an interaction of their frontier molecular orbitals. siRNA-mediated knockdown of cystathionine c-lyase attenuated migration of vascular endothelial cells induced by VEGF or moderate hypoxia.
Heme oxygenase-1 (HO-1) has anti-inflammatory effects in asthma. CD4+CD25high regulatory T cells (Treg) are a potent immunoregulator that suppresses the immune response. We studied the effects of HO-1-mediated CD4+CD25high Treg on suppression of allergic airway inflammation by comparing mice treated with hemin, OVA, Sn-protoporphyrin (SnPP), and hemin plus SnPP. Airway responsiveness, airway eosinophil infiltration, the level of OVA-specific IgE, and the numbers of cells in general and eosinophils in particular in bronchial alveolar lavage fluid were lower in the hemin group than in the OVA, SnPP, and hemin plus SnPP groups. The expressions of HO-1 mRNA and protein in the lung were increased by repeated administrations of hemin and SnPP. However, the activity of HO-1 was highest in hemin mice. The percentage and suppressive function of CD4+CD25high Treg and the expression of Foxp3 mRNA were obviously enhanced after treatment with hemin. This increase was diminished by the administration of SnPP. The concentration of serum IL-10 was higher in the hemin group than in the other groups, whereas the level of serum TGF-β did not significantly differ across groups. Furthermore, the ratio of IFN-γ/IL-4 mRNA in the lung was higher in hemin-treated mice than in OVA and SnPP mice. The suppressive capacity of CD4+CD25high Treg was not enhanced in the IL-10-deficient mice treated with hemin. In conclusion, our experiments in the animal model demonstrated that HO-1 has anti-inflammatory effects, probably via enhancement of the secretion of IL-10 and promotion of the percentage of CD4+CD25high Treg.
We previously proposed a new strategy to fabricate a novel foldable capsular vitreous body (FCVB) as a vitreous substitute and found that the FCVB was a very good replacement for closely mimicking the morphology and restoring the physiologic function of the rabbit vitreous body. The aim of this article was to assess the mechanical, optical, and biocompatible properties of a FCVB made from liquid silicone rubber. The mechanical properties show that the shore hardness is 37.80 degrees, the tear strength is 47.14 N/mm, the tensile strength is more than 7.28 MPa, and the elongation ratio is more than 1200%; in addition, the FCVB has 300 nm mili apertures in the capsule. The optical properties reveal that transmittances are 92%, hazes are 5.74%, and spectral transmittance is 97%. The transmittance mission is 2.3% and can sustain a 1500 mW, 0.2 s, 532 nm green laser. The biocompatible properties are shown in the stable extracts experiment, no significant fever, good genetic safety, and no structural abnormality or apoptosis in the cornea, ciliary body, and retina over a 6-month observation period. These results indicate that the FCVB has good mechanical, optical, and biocompatible properties, and the assessment results can be recommended as the FCVB technical standards for industrial manufacturing and inspection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.