Diabetes mellitus is considered to be a major risk factor for cardiovascular disease, the most common cause of death in diabetes. However, therapeutic strategies for myocardial protection in patients with diabetes are still limited. Cordycepin is a traditional Tibetan medicine with a long history of widespread use, and exerts a wide range of anti-tumor, anti-inflammatory, and anti-oxidative effects. In recent years, although the therapeutic potential of cordycepin has attracted the attention of researchers, it remains unknown whether cordycepin plays a protective role in myocardial ischemia/reperfusion (MI/R) injury in diabetic patients. Here, using a diabetic mouse model, we found that cordycepin protected diabetic hearts from MI/R injury by promoting mitochondrial fusion and Mfn2 expression. Our in vitro results showed that cordycepin enhanced Mfn2-medicated mitochondrial fusion, improved mitochondrial function, and reduced cardiomyocyte apoptosis in high-glucose/high-fat cultured simulated ischemia/reperfusion cardiomyocytes. Furthermore, we found that knockout of Mfn2 significantly blocked the cardioprotective effects of cordycepin in diabetic mice. Finally, an AMPK-dependent pathway was found to upregulate Mfn2 expression upon cordycepin treatment, indicating that cordycepin protected diabetic hearts via AMPK/Mfn2-dependent mitochondrial fusion. Collectively, our study firstly demonstrated that cordycepin could be a potential cardioprotective agent for MI/R injury, and we established a novel mechanism by which upregulated AMPK/Mfn2-dependent mitochondrial fusion contributes to the cardioprotective role of cordycepin.

Wound healing is related to proliferation, migration, and angiogenesis of keratinocytes. Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is an important N6-methyladenosine (m6A) reader, which is involved in multiple processes, including wound healing. However, the function and mechanism of IGF2BP2 in keratinocyte processes are largely uncertain. In the present study, expression levels of IGF2BP2 and heparanase (HPSE) were detected by quantitative reverse transcription polymerase chain reaction and western blotting assays. Cell proliferation was investigated by cell counting kit-8 (CCK-8) analysis. Cell migration was determined through wound healing assay. Angiogenesis was measured by tube formation assay and vascular endothelial growth factor (VEGF) level using enzyme linked immunosorbent assay (ELISA). The interaction between IGF2BP2 and HPSE was analyzed by RNA immunoprecipitation, pull-down and luciferase reporter analyses. The results showed that IGF2BP2 expression was enhanced in wound healing. IGF2BP2 downregulation constrained HaCaT cell proliferation, migration, and angiogenesis. IGF2BP2 knockdown decreased HPSE expression. IGF2BP2 could regulate HPSE stability by binding with 3ʹ untranslated region (UTR) of HPSE. HPSE upregulation attenuated silencing IGF2BP2-mediated suppression of proliferation, migration, and angiogenesis. As a conclusion, IGF2BP2 knockdown repressed proliferation, migration, and angiogenesis of HaCaT cells by decreasing HPSE stability.

Background:The children of depressed parents are more likely to suffer from mental illness, particularly major depressive disorder (MDD). However, most data come from adolescent and young-adult populations, and published studies have reported inconsistent results regarding intergenerational transmission. Material/Methods:We retrospectively investigated hospitalized depressed patients with positive family history (FHP) from 1 Jan 2008 to 31 Dec 2017 and analyzed the differences in sex distribution in the intergenerational transfer risk of major depressive disorder. Results:We enrolled 528 patients with maternal or paternal positive FHP from a total of 4856 patients, and divided them into 4 groups: female patients with maternal FHP (FM: 220, 41.7%), female patients with paternal FHP (FP: 116, 22.0%), male patients with maternal FHP (MM: 96, 18.2%), and male patients with paternal FHP (MP: 96, 18.2%).In this study, 12.2% of hospitalized depressed patients had an FHP. The ratio of male: female patients with FHP was 2: 3. The ratio of male: female patients with maternal FHP was almost 1: 2. Analyses showed that the risk of depression in daughters was higher than in sons. Compared with children of depressed fathers, the children of depressed mothers were at higher risk of depression. Daughters and sons share an equal risk of depression with paternal FHP. Conclusions:The results suggest a clear interaction of sex between patients and their depressed parents. Daughters of depressed mothers had the highest risk of suffering from depression compared with other offspring.