FGF2 Translationally Induced by Hypoxia Is Involved in Negative and Positive Feedback Loops with HIF-1α

BACKGROUND: Fibroblast growth factor 2 (FGF2) is a major angiogenic factor involved in angiogenesis and arteriogenesis, however the regulation of its expression during these processes is poorly documented. FGF2 mRNA contains an internal ribosome entry site (IRES), a translational regulator expected to allow mRNA expression during cellular stress. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have developed a skin ischemia model in transgenic mice expressing a reporter transgene under the control of the FGF2 IRES. The results reveal that FGF2 is induced at the protein level during ischemia, concomitant with HIF-1alpha induction and a decrease in FGF2 mRNA. In addition, the FGF2 IRES is strongly activated under these ischemic conditions associated with hypoxia, whereas cap-dependent translation is repressed by 4E-BP hypophosphorylation. We also show that up-regulation of FGF2 protein expression in response to hypoxia correlates with the increase of FGF2 IRES activity in vitro, in human retinoblasts 911. The use of siRNAs targeting HIF or FGF2 indicates that FGF2 and HIF-1alpha reciprocally regulate their expression/accumulation, by a negative feedback loop in early hypoxia, followed by a positive feedback loop in late hypoxia. CONCLUSION/SIGNIFICANCE: FGF2 expression is up-regulated in vivo and in vitro in response to hypoxia. Strikingly, this up-regulation is not transcriptional. It seems to occur by an IRES-dependent mechanism, revealing new mechanistic aspects of the hypoxic response. In addition, our data show that FGF2 interacts with HIF-1alpha in a unique crosstalk, with distinct stages in early and late hypoxia. These data reveal the physiological importance of IRES-dependent translation during hypoxic stress and underline the complexity of the cellular response to hypoxia, suggesting a novel role of FGF2 in the regulation of HIF-1alpha during the induction of angiogenesis

P559: HUMORAL RESPONSE TO MRNA-BASED COVID-19 VACCINE IN PATIENTS WITH MYELOID MALIGNANCIES

Data on the response to the COVID‐19 vaccine in patients with myeloid malignancy, who are at severe risk in case of infection, have not emerged. In a study of 69 patients with myeloid malignancies, including 46 patients with acute myeloid leukaemia (AML) and 23 patients with myelodysplastic syndrome (MDS), anti‐spike SARS‐CoV‐2 antibody titres were measured 3 months after the second mRNA‐based vaccination. Seroconversion rates for AML and MDS were 94.7% and 100% respectively, with no significant difference from healthy controls (HCs). Patients with MDS showed a significantly lower antibody titre than that in HCs or AML patients. In AML patients, the antibody titres were comparable to those in HCs when treatment was completed, but lower in patients under maintenance therapy. The response to COVID‐19 vaccine appears to be related to disease and treatment status. Patients with myeloid malignancies may be more responsive to vaccines than patients with lymphoid malignancies

Low Temperature Deposition of TiO₂ Thin Films through Atmospheric Pressure Plasma Jet Processing

Titanium dioxide (TiO2) has been widely used as a catalyst material in different applications such as photocatalysis, solar cells, supercapacitor, and hydrogen production, due to its better chemical stability, high redox potential, wide band gap, and eco-friendly nature. In this work TiO2 thin films have been deposited onto both glass and silicon substrates by the atmospheric pressure plasma jet (APPJ) technique. The structure and morphological properties of TiO2 thin films are studied using different characterization techniques like X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and field emission scanning electron microscopy. XRD study reveals the bronze-phase of TiO2. The XPS study shows the presence of Ti, O, C, and N elements. The FE-SEM study shows the substrate surface is well covered with a nearly round shaped grain of different size. The optical study shows that all the deposited TiO2 thin films exhibit strong absorption in the ultraviolet region. The oleic acid photocatalytic decomposition study demonstrates that the water contact angle decreased from 80.22 to 27.20° under ultraviolet illumination using a TiO2 photocatalyst