HMGB1-RAGE axis contributes to myocardial ischemia/reperfusion injury via regulation of cardiomyocyte autophagy and apoptosis in diabetic mice.

Patients with acute myocardial infarction complicated with diabetes are more likely to develop myocardial ischemia/reperfusion (I/R) injury (MI/RI) during reperfusion therapy. Both HMGB1 and RAGE play important roles in MI/RI. However, the specific mechanisms of HMGB1 associated with RAGE are not fully clarified in diabetic MI/RI. This study aimed to investigate whether the HMGB1-RAGE axis induces diabetic MI/RI via regulating autophagy and apoptosis. A db/db mouse model of MI/RI was established, where anti-HMGB1 antibody and RAGE inhibitor (FPS-ZM1) were respectively injected after 10 min of reperfusion. The results showed that treatment with anti-HMGB1 significantly reduced the infarct size, serum LDH, and CK-MB level. Similar situations also occurred in mice administrated with FPS-ZM1, though the HMGB1 level was unchanged. Then, we found that treatment with anti-HMGB1 or FPS-ZM1 performed the same effects in suppressing the autophagy and apoptosis, as reflected by the results of lower LAMP2 and LC3B levels, increased Bcl-2 level, reduced BAX and caspase-3 levels. Moreover, the Pink1/Parkin levels were also inhibited at the same time. Collectively, this study indicates that the HMGB1-RAGE axis aggravated diabetic MI/RI via apoptosis and Pink1/Parkin mediated autophagy pathways, and inhibition of HMGB1 or RAGE contributes to alleviating those adverse situations.

Identification of the relationships between sagittal plane and coronal plane curvature in guppy models.

OBJECTIVE: To explore the relationship between sagittal plane and coronal plane curvatures in guppies by investigating the curvature angles of sagittal and sagittal-coronal guppies. METHODS: After mating between 1000 spinal curvature guppies, 124 guppies (3-month old) were screened from progenies for the present study. Photos of all fishes were taken and the sagittal and coronal angles were calculated via angle measure tool of Photoshop 12.0 software. All data were analyzed by SPSS 11.0. RESULTS: In sagittal and sagittal-coronal curvature guppies, there was a significant linear correlation between sagittal angles and coronal angles. In 48 sagittal-coronal curvatures, their sagittal angles were above 40°, meanwhile, in 76 sagittal guppies, their sagittal angles were mostly below 40°. CONCLUSIONS: These findings indicated that the occurrence of coronal curvature might be later than sagittal curvature and could be influenced by other factors. Sagittal angles 40° might be involved in the onset of coronal curvature.