Characterization of a novel glutamate dehydrogenase gene and its response to heat stress in the sea urchin Strongylocentrotus intermedius

Glutamate dehydrogenase (GDH), a key metabolic enzyme that is ubiquitous across almost all living species, is essential for cell survival. To elucidate the characteristics and functions of the GDH gene in the sea urchin, we cloned and characterized the full-length cDNA of a novel GDH homolog from Strongylocentrotus intermedius, herein designated SiGDH. The full-length SiGDH gene was 2499 bp, with an open reading frame (ORF) of 1635 bp, encoding 544 amino acids. Bioinformatic analyses revealed that the predicted SiGDH protein contained the conserved ELFV_dehydrog_N and ELFV_dehydrog domains and that this protein had the highest sequence identity with the GDH protein from Strongylocentrotus purpuratus. Tissue-specific differences in SiGDH relative expression patterns and enzyme activity levels were observed, and the highest relative expression and total enzyme activity of SiGDH were determined to be in the gonad. Changes in SiGDH relative expression and enzyme activity in the gonad were observed after both gradual and acute heat stress. Together, our observations help to clarify the characteristics of this GDH homolog, as well as its associations with heat resistance in echinoderms

The Effect of CM082, an Oral Tyrosine Kinase Inhibitor, on Experimental Choroidal Neovascularization in Rats

The aims of this study were to evaluate the effects of CM082 on the development of choroidal neovascularization (CNV) in a laser-induced CNV rat model and to determine the drug concentration in the ocular tissues. After the laser-induced CNV model was established in rats, CM082 was orally administered. The effects of CM082 on the CNV lesions were assessed using fundus fluorescein angiography (FFA), CNV histology, and retinal pigment epithelium- (RPE-) choroid-sclera eyecup analysis. The concentrations of CM082 in the plasma and eye tissues were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results of FFA, histology, and RPE-choroid-sclera eyecup analysis demonstrated that the CM082-treated (10 mg/kg/d or 30 mg/kg/d) rats exhibited significantly less neovascularization than did the control group. The total concentration of CM082 in the eyes (172.86 ± 57.11 ng/g) was similar to that in the plasma (196.87 ± 73.13 ng/ml). Within the eye, the concentrations of CM082 and its metabolites were highest in the retina-sclera. The orally administered CM082 thus effectively passed through the blood-retina barrier (BRB) to reach the retina in the Brown Norway rats. Therefore, at both 10 mg/kg/d and 30 mg/kg/d, CM082 was able to reduce CNV lesions in the laser-induced CNV rat model

Circulating miRNAs as Potential Biomarkers of Age-Related Macular Degeneration

Backgroud: Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness of the elder people. This research was intended to demonstrate the different expression of microRNAs (miRNA) in AMD patients and whether they can be used as biomarkers for AMD. Methods: MiRNAs expression was measured by microarray of 6 AMD cases and 6 gender matched controls. In a larger-sample case-control study with 126 AMD cases and 140 controls, whole blood samples were detected for the differences of miRNA expression. Results: A total of 216 differentially expressed miRNAs (111 increased and 105 decreased miRNAs) were detected from circulating miRNA microarray. Expanded case-control study results showed that the expression of miR-27a-3p, miR-29b-3p and miR-195-5p was increased significantly. Moreover, the level of miR-27a is higher in patients with wet AMD compared to patients with dry AMD. All 3 miRNAs showed a potential diagnostic value for AMD. Conclusion: Circulating miRNA levels were significantly varied in AMD patients. Three miRNAs, miR-27a-3p, miR-29b-3p and the miR-195-5p, might be potential diagnostic biomarkers for AMD

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization

Abstract Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization. Graphical Abstrac

Selective Polarization Modification of Upconversion Luminescence of NaYF₄:Yb³⁺,Er³⁺ Nanoparticles by Plasmonic Nanoantenna Arrays

Rare-earth ions doped upconversion nanoparticles (UCNPs) have received great attention for the promising applications ranging from bioimaging and sensing to lighting and displaying technology. Meanwhile, active control of polarization state of the upconversion luminescence (UCL) of UCNPs is also significant in the applications such as polarization microscopy and 3D display. Here, we report the polarization modification for the UCL of β-NaYF₄:Yb³⁺,Er³⁺ nanoparticles by selectively matching the localized surface plasmon resonance (LSPR) of the rectangular plasmonic slot nanoantenna array to the spectrum of the UCL. The plasmonic resonance band centered at 650 nm of the nanoantenna array realized a strong polarization nature of the selected UCL around 660 nm with the degree of linear polarization up to ∼80%, which stems from the interaction between the 660 nm emission band of UCNPs and the plasmonic modes of the rectangular slot nanoantenna array. Meanwhile, the UCL at 550 nm remained unpolarized due to the mismatch to the plasmonic modes. The experimental results are explained well by theoretical simulations based on the local surface plasmonic resonance. Our results provide an effective way to control the anisotropic UCL of UCNPs with the applications in polarization-based imaging and 3D display technologies and so forth