Syringin is found in the root of Acanthopanax senticosus(Rupr.Maxim.)Harms and belongs to the lignin chemical compound with many biological activities.In this study,we employed commercially available starting material...Syringin is found in the root of Acanthopanax senticosus(Rupr.Maxim.)Harms and belongs to the lignin chemical compound with many biological activities.In this study,we employed commercially available starting materials and accomplished the total synthesis of syringin in 5 steps with an overall yield of 58%.Palladium-catalyzed C(O)–C bond activation and subsequent cross coupling reaction is the key to construct syringin and its natural analogues.展开更多
Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-met...Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
基金supported by the Shanghai Institute of Materia Medica,the Chinese Academy of Sciences,the National Natural Science Foundation of China(21772211,21920102003)the Institutes for Drug Discovery and Development,Chinese Academy of Sciences(CASIMM0120163006)+2 种基金the Science and Technology Commission of Shanghai Miunicipality(17JC1405000,18431907100)the Program of Shanghai Academic Research Leader(19xD1424600)the National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(2018ZX09711002-006).
文摘Syringin is found in the root of Acanthopanax senticosus(Rupr.Maxim.)Harms and belongs to the lignin chemical compound with many biological activities.In this study,we employed commercially available starting materials and accomplished the total synthesis of syringin in 5 steps with an overall yield of 58%.Palladium-catalyzed C(O)–C bond activation and subsequent cross coupling reaction is the key to construct syringin and its natural analogues.
基金supported by the National Natural Science Foundation of China,Nos.82030071 (to JH),82272495 (to YC)Science and Technology Major Project of Changsha,No.kh2103008 (to JH)Graduate Students’ Independent Innovative Projects of Hunan Province,No.CX20230311 (to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
