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- Lee, Chunsik, et al.
(författare)
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VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway
- 2023
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Ingår i: SIGNAL TRANSDUCTION AND TARGETED THERAPY. - : SPRINGERNATURE. - 2095-9907 .- 2059-3635. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.
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- Hu, Xialin, et al.
(författare)
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DEVELOPMENT OF NEGLIGIBLE DEPLETION HOLLOW FIBER-PROTECTED LIQUID-PHASE MICROEXTRACTION FOR SENSING FREELY DISSOLVED TRIAZINES
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 28:2, s. 231-238
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Tidskriftsartikel (refereegranskat)abstract
- A new sampling method, termed negligible depletion hollow fiber-protected liquid-phase microextraction, was developed for sensing the freely dissolved concentration (C free) and evaluating the availability of atrazine (ATR), desethyl atrazine (DEA), and simazine (SIM) in water. The sampling device was prepared by impregnating 1-octanol to both the pores and the lumen of a piece of polypropylene microporous hollow fiber membrane. After equilibrium and negligible depletion extraction, the 1-octanol in the lumen of the hollow fiber (10 mu l) was collected for determination of triazines. Determination of C free and the distribution coefficient to 1-octanol (D-OW) can be performed with this technique. A wide linear working range (1-200 mu g/L) and low detection limits (0.1-1 mu g/L) were obtained for triazines. Measured log D-OW values of DEA (1.44 +/- 0.04), SIM (2.06 +/- 0.06), and ATR (2.33 +/- 0.05) agreed well with those reported in the literature. The measured D-OW values were independent of the chemical concentration and sample pH (pH 3-10) and negligibly affected by the sample salinity (0-500 mM), suggesting that environmentally relevant pH and salinity have no significant effects on the availability of triazines. Although a slight (<= 31%) increase of C free was observed, one-way analysis of variance indicated the C free of triazines were not significantly affected by the presence of Aldrich humic acid, Acros humic acid, and bovine albumin V (dissolved organic carbon [DOC], 0-100 mg/L). From 3 to 36% of the spiked triazines, however, were found to associate with the dissolved organic matter (DOM) in surface-water samples (DOC, 32.0-61.9 mg/L), suggesting the origin of the DOM is a key parameter in determining its association with and, thus, the availability of triazines.
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