Grpel2 maintains cardiomyocyte survival in diabetic cardiomyopathy through DLST-mediated mitochondrial dysfunction: a proof-of-concept study.

BACKGROUND: Diabetic cardiomyopathy (DCM) has been considered as a major threat to health in individuals with diabetes. GrpE-like 2 (Grpel2), a nucleotide exchange factor, has been shown to regulate mitochondrial import process to maintain mitochondrial homeostasis. However, the effect and mechanism of Grpel2 in DCM remain unknown. METHODS: The streptozotocin (STZ)-induced DCM mice model and high glucose (HG)-treated cardiomyocytes were established. Overexpression of cardiac-specific Grpel2 was performed by intramyocardial injection of adeno-associated virus serotype 9 (AAV9). Bioinformatics analysis, co-immunoprecipitation (co-IP), transcriptomics profiling and functional experiments were used to explore molecular mechanism of Grpel2 in DCM. RESULTS: Here, we found that Grpel2 was decreased in DCM induced by STZ. Overexpression of cardiac-specific Grpel2 alleviated cardiac dysfunction and structural remodeling in DCM. In both diabetic hearts and HG-treated cardiomyocytes, Grpel2 overexpression attenuated apoptosis and mitochondrial dysfunction, including decreased mitochondrial ROS production, increased mitochondrial respiratory capacities and increased mitochondrial membrane potential. Mechanistically, Grpel2 interacted with dihydrolipoyl succinyltransferase (DLST), which positively mediated the import process of DLST into mitochondria under HG conditions. Furthermore, the protective effects of Grpel2 overexpression on mitochondrial function and cell survival were blocked by siRNA knockdown of DLST. Moreover, Nr2f6 bond to the Grpel2 promoter region and positively regulated its transcription. CONCLUSION: Our study provides for the first time evidence that Grpel2 overexpression exerts a protective effect against mitochondrial dysfunction and apoptosis in DCM by maintaining the import of DLST into mitochondria. These findings suggest that targeting Grpel2 might be a promising therapeutic strategy for the treatment of patients with DCM.

Effectiveness of calamine lotion as an adjunctive therapy to mometasone furoate ointment in the treatment of infant eczema: A retrospective study.

This retrospective study investigated the effectiveness of calamine lotion (CL) as an adjunctive therapy to mometasone furoate ointment (MFO) in the treatment of infant eczema (IE). This retrospective study analyzed the electronic medical records of 50 IE infants. They were allocated to a treatment group or a control group, with 25 subjects in each group. All infants in both groups received MFO. In addition, infants in the treatment group underwent CL. The outcomes were effectiveness based on the eczema area and severity index, lesion area, and pruritus severity. We analyzed the outcomes before and after treatment. The results of this study showed that infants in the treatment group had more effective in effectiveness based on eczema area and severity index (P < .01), lesion area (P < .01), and pruritus severity (P = .01) than those in the control group. However, no medical records reported any adverse events in either group. The results of this study showed that CL added to MFO was more effective than MFO alone in the treatment of infants with IE.