RESUMO
ABSTACT: With advancing age, the incidence of sarcopenia increases, eventually leading to a cascade of adverse events. However, there is currently a lack of effective pharmacological treatment for sarcopenia. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) empagliflozin demonstrates anti-fibrotic capabilities in various organs. This study aims to determine whether empagliflozin can improve skeletal muscle fibrosis induced by sarcopenia in naturally aging mice. A natural aging model was established by feeding male mice from 13 months of age to 19 months of age. A fibrosis model was created by stimulating skeletal muscle fibroblasts with TGF-ß1. The Forelimb grip strength test assessed skeletal muscle function, and expression levels of COL1A1, COL3A1, and α-SMA were analyzed by western blot, qPCR, and immunohistochemistry. Additionally, levels of AMPKα/MMP9/TGFß1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle function declines, expression of muscle fibrosis markers increases, AMPKα expression is downregulated, and MMP9/TGFß1/Smad signaling pathways are upregulated. However, treatment with empagliflozin reverses this phenomenon. At the cellular level, empagliflozin exhibits similar anti-fibrotic effects, and these effects are attenuated by Compound C and siAMPKα. Empagliflozin exhibits anti-fibrotic effects, possibly associated with the AMPK/MMP9/TGFß1/Smad signaling pathways.
Assuntos
Proteínas Quinases Ativadas por AMP , Envelhecimento , Compostos Benzidrílicos , Fibrose , Glucosídeos , Metaloproteinase 9 da Matriz , Músculo Esquelético , Transdução de Sinais , Proteínas Smad , Inibidores do Transportador 2 de Sódio-Glicose , Fator de Crescimento Transformador beta1 , Animais , Masculino , Glucosídeos/farmacologia , Compostos Benzidrílicos/farmacologia , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Sarcopenia/tratamento farmacológico , Sarcopenia/metabolismo , Sarcopenia/prevenção & controle , Sarcopenia/patologia , Camundongos Endogâmicos C57BLRESUMO
Here, we report a gold-furnished mesh as the current collector for Zn electrodeposition, which is used as the anode in aqueous zinc-ion batteries. The anode exhibits excellent cycling performance without obvious dendrite growth, and the full cell shows an outstanding specific capacity and long-term durability, surpassing those of bare Zn.
RESUMO
Synthetic microbial communities have emerged as an attractive route for chemical bioprocessing. They are argued to be superior to single strains through microbial division of labor (DOL), but the exact mechanism by which DOL confers advantages remains unclear. Here, we utilize a synthetic Saccharomyces cerevisiae consortium along with mathematical modeling to achieve tunable mixed sugar fermentation to overcome the limitations of single-strain fermentation. The consortium involves two strains with each specializing in glucose or xylose utilization for ethanol production. By controlling initial community composition, DOL allows fine tuning of fermentation dynamics and product generation. By altering inoculation delay, DOL provides additional programmability to parallelly regulate fermentation characteristics and product yield. Mathematical models capture observed experimental findings and further offer guidance for subsequent fermentation optimization. This study demonstrates the functional potential of DOL in bioprocessing and provides insight into the rational design of engineered ecosystems for various applications.