Doxorubicin (DOX) is known as an effective drug in the fight against various cancers. However, one of the greatest impediments is DOX-induced cardiomyopathy, which may potentially lead to heart failure. Accumulating evidence has shed light on the pathological mechanism of DOX-induced cardiotoxicity, but treatments to mitigate the cardiac damage are still required. In an attempt to address this issue, we evaluated whether exercise provides cardioprotective effects on the DOX-induced cardiotoxicity. We showed that treadmill exercise (3 times/week; 1-week of exercise acclimatization and 4-weeks of endurance exercise) during the DOX treatment successfully prevented the cardiac dysfunction. The DOX-stimulated expression of IκBα, NF-κB, COX-2, and IL-8 were all downregulated by exercise as well as the fibrosis factors (TGF-β1, phosphorylated ERK, Sp1, and CTGF). Moreover, we showed that treadmill exercise diminished the expression of several cardiac remodeling-associated factors, such as FGF2, uPA, MMP2, and MMP9. These results were in line with the finding that exercise intervention reduced cardiac fibrosis and restored cardiac function, with higher values of ejection fraction and fractional shortening compared to the DOX-treated group. Two commonly used indicators of cardiac injury, lactate dehydrogenase, and creatine kinase-MB, were also decreased in the exercise group. Collectively, our results suggested that it may be beneficial to prescribe treadmill exercise as an adjunct therapy to limit cardiac damage caused by DOX.

Galectin‐3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin‐3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin‐like oxidized low‐density lipoprotein (oxLDL) receptor‐1 (LOX‐1), a receptor for oxLDL uptake, contributes to oxLDL‐induced endothelial dysfunction. Whether galectin‐3 induces endothelial dysfunction through modulation of LOX‐1‐mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin‐3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX‐1. Incubation of HUVECs with galectin‐3 increased the expression of LOX‐1 in RNA and protein levels. In addition, the expression of LOX‐1 induced by oxLDL was promoted by galectin‐3. However, pretreatment of LOX‐1 antibody reduced LOX‐1 mRNA expression level in cells with oxLDL plus galectin‐3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen‐activated protein kinases followed by nuclear factor kappa B (NF‐κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL‐8 release were also aggravated in cells treated with galectin‐3 combined with oxLDL. Compared to cells treated with galectin‐3 plus oxLDL group. We found that LOX‐1 antibody mitigated NADPH oxidase activity, p‐38 up‐regulation, NF‐κB activation, and proinflammatory responses in cells treated with galectin‐3 combined with oxLDL. We conclude that galectin‐3 enhances endothelial LOX‐1 expression and propose a new mechanism by which galectin‐3 may promote endothelial dysfunction by inducing inflammation via LOX‐1/ROS/p38/NF‐κB‐mediated signaling pathway.

The sand-blasting and acid etching (SLA) method can fabricate a rough topography for mechanical fixation and long-term stability of titanium implant, but can not achieve early bone healing. This study used two kinds of plasma treatments (Direct-Current and Radio-Frequency plasma) to modify the SLA-treated surface. The modification of plasma treatments creates respective power range and different content functional OH groups. The results show that the plasma treatments do not change the micron scale topography, and plasma-treated specimens presented super hydrophilicity. The X-ray photoelectron spectroscopy (XPS)-examined result showed that the functional OH content of the RF plasma-treated group was higher than the control (SLA) and DC treatment groups. The biological responses (protein adsorption, cell attachment, cell proliferation, and differentiation) promoted after plasma treatments, and the cell responses, have correlated to the total content of amphoteric OH groups. The experimental results indicated that plasma treatments can create functional OH groups on SLA-treated specimens, and the RF plasma-treated SLA implant thus has potential for achievement of bone healing in early stage of implantation.

Background Emerging evidence demonstrated dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, prevented various cardiovascular events. However, the detailed mechanisms underlying its cardioprotective properties remained largely unknown. Results In the present study, we sought to investigate the effects of DAPA on the cardiac ischemia/reperfusion (I/R) injury. Results from in vitro experiments showed that DAPA induced the phosphorylation of AMPK, resulting in the downregulation of PKC in the cardiac myoblast H9c2 cells following hypoxia/reoxygenation (H/R) condition. We demonstrated that DAPA treatment diminished the H/R-elicited oxidative stress via the AMPK/ PKC/ NADPH oxidase pathway. In addition, DAPA prevented the H/R-induced abnormality of PGC-1α expression, mitochondrial membrane potential, and mitochondrial DNA copy number through AMPK/ PKC/ NADPH oxidase signaling. Besides, DAPA reversed the H/R-induced apoptosis. Furthermore, we demonstrated that DAPA improved the I/R-induced cardiac dysfunction by echocardiography and abrogated the I/R-elicited apoptosis in the myocardium of rats. Also, the administration of DAPA mitigated the production of myocardial infarction markers. Conclusions In conclusion, our data suggested that DAPA treatment holds the potential to ameliorate the I/R-elicited oxidative stress and the following cardiac apoptosis via modulation of AMPK, which attenuates the cardiac dysfunction caused by I/R injury.

No abstract