We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More impor...We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.展开更多
Anthocyanins are important flavonoid pigments in the coloration of fruits.To identify candidate genes involved in anthocyanin accumulation,metabolic and transcriptome analyses were conducted in‘Nanguo'pear and it...Anthocyanins are important flavonoid pigments in the coloration of fruits.To identify candidate genes involved in anthocyanin accumulation,metabolic and transcriptome analyses were conducted in‘Nanguo'pear and its red sport cultivar‘Nanhong'pear.The results showed that‘Nanhong'pear had significantly higher anthocyanin and flavonol contents.Additionally,transcriptomic analysis showed that there were significant differences in the expression of genes involved in phenylpropanoid and flavonoid biosynthesis pathways between the two cultivars,with PuGSTF12 being the most upregulated gene in the‘Nanhong'cultivar.Further analysis identified a novel MYB transcription factor(PuMYB93),and its silencing repressed PuGSTF12 expression and anthocyanin accumulation,suggesting it plays an essential role in the regulation of anthocyanin biosynthesis.Moreover,yeast one-hybrid analysis,electrophoretic mobility shift assay,andβ-glucuronidase assay indicated that PuMYB93 can directly bind to the PuGSTF12 promoter to positively regulate its expression.Additionally,PuGSTF12 silencing suppressed the coloration of PuMYB93-OE peels,suggesting that PuGSTF12 act downstream of PuMYB93.Overall,the findings of this study show that PuMYB93 promotes anthocyanin transport in pears by regulating PuGSTF12 expression to further enhance anthocyanin accumulation.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 82071304 (to QXZ), 81671149 (to QXZ),and 81971179 (to XML)the Natural Science Foundation of Jiangsu Province,Nos. BK20191463 (to XML) and BK20161167 (to QXZ)。
文摘We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.
基金supported by the National Natural Science Foundation of China(32372641)the Shandong Provincial Natural Science Foundation,China(ZR2024QC143)the Liaoning Provincial Natural Science Foundation,China(2022-MS-258)。
文摘Anthocyanins are important flavonoid pigments in the coloration of fruits.To identify candidate genes involved in anthocyanin accumulation,metabolic and transcriptome analyses were conducted in‘Nanguo'pear and its red sport cultivar‘Nanhong'pear.The results showed that‘Nanhong'pear had significantly higher anthocyanin and flavonol contents.Additionally,transcriptomic analysis showed that there were significant differences in the expression of genes involved in phenylpropanoid and flavonoid biosynthesis pathways between the two cultivars,with PuGSTF12 being the most upregulated gene in the‘Nanhong'cultivar.Further analysis identified a novel MYB transcription factor(PuMYB93),and its silencing repressed PuGSTF12 expression and anthocyanin accumulation,suggesting it plays an essential role in the regulation of anthocyanin biosynthesis.Moreover,yeast one-hybrid analysis,electrophoretic mobility shift assay,andβ-glucuronidase assay indicated that PuMYB93 can directly bind to the PuGSTF12 promoter to positively regulate its expression.Additionally,PuGSTF12 silencing suppressed the coloration of PuMYB93-OE peels,suggesting that PuGSTF12 act downstream of PuMYB93.Overall,the findings of this study show that PuMYB93 promotes anthocyanin transport in pears by regulating PuGSTF12 expression to further enhance anthocyanin accumulation.
