GSK621 attenuates oxygen glucose deprivation/re-oxygenation-induced myocardial cell injury via AMPK-dependent signaling.

Recent studies have implied that activation of AMP-dependent protein kinase (AMPK) could protect myocardial cells from oxygen glucose deprivation-re-oxygenation (OGD/R). The aim of the present study is to test whether GSK621, a novel and direct AMPK activator, could exert myocardial cell protection against OGD/R. We show that in AC16 human myocardial cells and primary murine myocardiocytes GSK621 dose-dependently activated AMPK signaling. GSK621 pretreatment potently inhibited OGD/R-induced viability reduction, cell death and apoptosis in AC16 cells and primary myocardiocytes. Furthermore, GSK621 attenuated OGD/R-induced reactive oxygen species production and oxidative injury in the myocardial cells. AMPKα1 knockdown (via targeted shRNA), knockout (via a CRISPR/Cas9 construct) or dominant negative mutation (T172A) not only blocked GSK621-induced AMPK activation, but also nullified GSK621-mediated myocardial cell protection against OGD/R. Further studies demonstrated that GSK621 activated AMPK downstream Nrf2 signaling. Contrarily, Nrf2 silencing by targeted shRNAs almost abolished GSK621-induced anti-OGD/R myocardial cell protection. We conclude that GSK621 protects myocardial cells from OGD/R through activation of AMPK-dependent signaling.

Effect of probucol on vascular remodeling due to atherosclerosis in rabbits: an intravascular ultrasound study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis.</p><p><b>METHODS</b>Aortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks' atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% (wt/wt) probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed.</p><p><b>RESULTS</b>Probucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group (56% vs. 21%, 18% vs. 54%, respectively, both P < 0.01). In addition, the probucol group showed a smaller mean remodeling index relative to the control group (0.93 ± 0.13 vs. 1.05 ± 0.16, P < 0.01). Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S (all P < 0.01).</p><p><b>CONCLUSIONS</b>These findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.</p>

Three-dimensional limited element analysis of the complication after resection of head of radius for adults / 医用生物力学

Objective To adopt a three-dimensional limited element analytic method to research into the cause and mechanism of the complications taking place after resection of head radius.Method To adopt a three-dimensional limited element analytic method to research into the stress transmission action of the head radi-us and the distribution alteration of the stress transmission after resection of head radius impacting on the stability of elbow and wrist.Result In normal cases,the stress value transmitted via head of radius takes 58% of the stress placed,36.85% via humeroulnar joint.The head of radius places a leading role in the stress transmission of the elbow joint.After rasection of the head of radius,the lateral of humeroulnar joint bears about 43% of the stress placed while the medial part bears about 21.6% of the stress.To compare with that before the resection of the head of radius the stress on the lateral is obviously increased more than the medial part.Conclusions The head of radius places a leading role in the stress transm ission of the el-bow joint.The resection of the head radius breaks the normal distribution of the stress on the elbow joint and produces great effect on the stability of the elbow joint and wrist joint.Therefore,in clinics we should pay great attention to the indication of rasection of the head of radius.

Three-dimensional limited element analysis of the complication after resection of head of radius for adults / 医用生物力学

Objective To adopt a three-dimensional limited element analytic method to research into the cause and mechanism of the complications taking place after resection of head radius.Method To adopt a three-dimensional limited element analytic method to research into the stress transmission action of the head radi-us and the distribution alteration of the stress transmission after resection of head radius impacting on the stability of elbow and wrist.Result In normal cases,the stress value transmitted via head of radius takes 58% of the stress placed,36.85% via humeroulnar joint.The head of radius places a leading role in the stress transmission of the elbow joint.After rasection of the head of radius,the lateral of humeroulnar joint bears about 43% of the stress placed while the medial part bears about 21.6% of the stress.To compare with that before the resection of the head of radius the stress on the lateral is obviously increased more than the medial part.Conclusions The head of radius places a leading role in the stress transm ission of the el-bow joint.The resection of the head radius breaks the normal distribution of the stress on the elbow joint and produces great effect on the stability of the elbow joint and wrist joint.Therefore,in clinics we should pay great attention to the indication of rasection of the head of radius.