Cystathionine ß-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3.

Lymphangiogenesis is a key player in several diseases such as tumor metastasis, obesity, and graft rejection. Endogenous regulation of lymphangiogenesis is only partly understood. Here we use the normally avascular cornea as a model to identify endogenous regulators of lymphangiogenesis. Quantitative trait locus analysis of a large low-lymphangiogenic BALB/cN x high-lymphangiogenic C57BL/6 N intercross and prioritization by whole-transcriptome sequencing identify a novel gene responsible for differences in lymphatic vessel architecture on chromosome 17, the cystathionine ß-synthase (Cbs). Inhibition of CBS in lymphatic endothelial cells results in reduce proliferation, migration, altered tube-formation, and decrease expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGF-R2) and VEGF-R3, but not their ligands VEGF-C and VEGF-D. Also in vivo inflammation-induced lymphangiogenesis is significantly reduce in C57BL/6 N mice after pharmacological inhibition of CBS. The results confirm CBS as a novel endogenous regulator of lymphangiogenesis acting via VEGF receptor 2 and 3-regulation and open new treatment avenues in diseases associated with pathologic lymphangiogenesis.

Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation.

Under normal conditions, the cornea, being the transparent "windscreen" of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation. Corneal transplantation is one of the most commonly performed transplantations worldwide, with more than 40,000 surgeries per year in Europe. To date, various anti-hem- and anti-lymphangiogenic treatment strategies have been developed specifically for the corneal vascular endothelial growth factor (VEGF) pathway. Currently, however, no treatment strategies are clinically available to specifically modulate lymphangiogenesis. In this review, we will give an overview about endogenous regulators of hem- and lymphangiogenesis and discuss potential new strategies for targeting pathological lymphangiogenesis. Furthermore, we will review recently identified modulators and demonstrate that the cornea is a suitable model for the identification of novel endogenous modulators of lymphangiogenesis. The identification of novel modulators of lymphangiogenesis and a better understanding of the signaling pathways involved will contribute to the development of new therapeutic targets for the treatment of pathological lymphangiogenesis. This, in turn, will improve graft rejection, not only for the cornea.

Antibacterial properties of nanoporous graphene oxide/cobalt metal organic framework.

Metal-organic framework (MOF) based graphene oxide (GO) recently merits of attention because of the relative correspondence of GO with metal ions and organic binding linkers. Furthermore, introducing the GO to the Co-MOF to make a new nanoporous hybrid have are improved the selectivity and stability of the Co-MOF. Here the graphene oxide/cobalt metal organic framework (GO/Co-MOF) was synthesized by a solvothermal process using cobalt salt and terephthalic acid and used for biocidal activity, against the growth of the Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. X-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy were confirmed the successful synthesize of metal organic framework and incorporation of Co-MOF in to GO sheets. Scanning electron microscopy was showed the cornflower structure of GO/Co-MOF, and transmission electron microscopy was confirmed, the Co-MOF are decorated on GO. Cytotoxicity study of GO/Co-MOF using 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) cell viability assay showed the biocompatibility to human fibroblasts cell over 72 h. The growth inhibition of the Escherichia coli and Staphylococcus aureus bacteria are reached over 99% for bacteria concentration of 100 µg/mL. The excellent antibacterial activity of GO based Co-MOF is linked to synergistic effect of sharp edges of the GO sheets and the toxic effect of cobalt ions (Co2+) which are released from their surfaces. The GO/Co-MOF radical scavenging assay was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant assay for samples incubated with cells which confirmed the minimum radicals' toxicity on bacteria. This novel graphene oxide based MOF with its intrinsic superior porous structure, highly active metal coordination, and commercial linker, is an excellent promising candidate to use in biological and pharmaceutical applications as high potential sustained bactericidal materials.