Exploring novel lead scaffolds for SGLT2 inhibitors: Insights from machine learning and molecular dynamics simulations
Int J Biol Macromol. 2024 Feb 23:130375. doi: 10.1016/j.ijbiomac.2024.130375. Online ahead of print.ABSTRACTSodium-glucose cotransporter 2 (SGLT2) plays a pivotal role in mediating glucose reabsorption within the renal filtrate, representing a well-known target in type 2 diabetes and heart failure. Recent emphasis has been directed toward designing SGLT2 inhibitors, with C-glycoside inhibitors emerging as front-runners. The architecture of SGLT2 has been successfully resolved using cryo-electron microscopy. However, comprehension of the pharmacophores within the binding site of SGLT2 remains unclear. Here, we use machine l...
Source: International Journal of Biological Macromolecules - February 25, 2024 Category: Biochemistry Authors: Yuandong Yu Yuting Xia Guizhao Liang Source Type: research
The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway
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-β1. 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/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle fu...
Source: Biogerontology - February 25, 2024 Category: Geriatrics Authors: Qixuan Huang Jie Chen Siqi Liao Jiangchuan Long Ronghua Fang Yusen He Peiyun Chen Dongfang Liu Source Type: research
Exploring novel lead scaffolds for SGLT2 inhibitors: Insights from machine learning and molecular dynamics simulations
Int J Biol Macromol. 2024 Feb 23:130375. doi: 10.1016/j.ijbiomac.2024.130375. Online ahead of print.ABSTRACTSodium-glucose cotransporter 2 (SGLT2) plays a pivotal role in mediating glucose reabsorption within the renal filtrate, representing a well-known target in type 2 diabetes and heart failure. Recent emphasis has been directed toward designing SGLT2 inhibitors, with C-glycoside inhibitors emerging as front-runners. The architecture of SGLT2 has been successfully resolved using cryo-electron microscopy. However, comprehension of the pharmacophores within the binding site of SGLT2 remains unclear. Here, we use machine l...
Source: International Journal of Biological Macromolecules - February 25, 2024 Category: Biochemistry Authors: Yuandong Yu Yuting Xia Guizhao Liang Source Type: research
The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway
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-β1. 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/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle fu...
Source: Biogerontology - February 25, 2024 Category: Geriatrics Authors: Qixuan Huang Jie Chen Siqi Liao Jiangchuan Long Ronghua Fang Yusen He Peiyun Chen Dongfang Liu Source Type: research
The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway
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-β1. 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/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle fu...
Source: Biogerontology - February 25, 2024 Category: Geriatrics Authors: Qixuan Huang Jie Chen Siqi Liao Jiangchuan Long Ronghua Fang Yusen He Peiyun Chen Dongfang Liu Source Type: research
The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway
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-β1. 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/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle fu...
Source: Biogerontology - February 25, 2024 Category: Geriatrics Authors: Qixuan Huang Jie Chen Siqi Liao Jiangchuan Long Ronghua Fang Yusen He Peiyun Chen Dongfang Liu Source Type: research
The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway
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-β1. 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/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle fu...
Source: Biogerontology - February 25, 2024 Category: Geriatrics Authors: Qixuan Huang Jie Chen Siqi Liao Jiangchuan Long Ronghua Fang Yusen He Peiyun Chen Dongfang Liu Source Type: research
The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway
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-β1. 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/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle fu...
Source: Biogerontology - February 25, 2024 Category: Geriatrics Authors: Qixuan Huang Jie Chen Siqi Liao Jiangchuan Long Ronghua Fang Yusen He Peiyun Chen Dongfang Liu Source Type: research
Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED)
ConclusionsThis trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function. (Source: Clinical and Experimental Nephrology)
Source: Clinical and Experimental Nephrology - February 25, 2024 Category: Urology & Nephrology Source Type: research
