An Ethylene-inhibited NF-YC Transcription Factor RhNF-YC9 Regulates Petal Expansion in Rose

The speed of flower opening is closely related to their ornamental period. Ethylene functions as a negative regulator involved in the regulation of the petal expansion process. In this study, we isolated a NF-YC transcription factor gene, RhNF-YC9, from rose petals. RhNF-YC9 expression was induced at the early stages of flower opening but was inhibited by ethylene treatment. Silencing RhNF-YC9 decreased the speed of petal expansion from stage 2 to stage 5. The expressions of 11 cell expansion-related genes involved in cell wall loosening, cell turgor modulation, and cytoskeleton remodeling were significantly down-regulated in RhNF-YC9-silenced petals. We also found that silencing RhNF-YC9 decreased the expression of gibberellin acid (GA) biosynthetic gene RhGA20ox while significantly increasing the transcripts of GA catabolic gene RhGA2ox, reducing the accumulation of GA4 and GA7. The influence of ethylene treatment on the expression of RhGA20ox and RhGA2ox showed the same trend. These results together suggested that RhNF-YC9 positively regulated the speed of petal expansion and mediated the crosstalk between ethylene and GA. Our findings revealed a new insight into the function of NF-YC transcription factors involved in ethylene-regulated petal expansion

Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

Abstract Background Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI

Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity

Summary: Enhancing chemosensitivity is one of the largest unmet medical needs in cancer therapy. Cyclic GMP-AMP synthase (cGAS) connects genome instability caused by platinum-based chemotherapeutics to type I interferon (IFN) response. Here, by using a high-throughput small-molecule microarray-based screening of cGAS interacting compounds, we identify brivanib, known as a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor, as a cGAS modulator. Brivanib markedly enhances cGAS-mediated type I IFN response in tumor cells treated with platinum. Mechanistically, brivanib directly targets cGAS and enhances its DNA binding affinity. Importantly, brivanib synergizes with cisplatin in tumor control by boosting CD8+ T cell response in a tumor-intrinsic cGAS-dependent manner, which is further validated by a patient-derived tumor-like cell clusters model. Taken together, our findings identify cGAS as an unprecedented target of brivanib and provide a rationale for the combination of brivanib with platinum-based chemotherapeutics in cancer treatment