Oxidative stress plays an important role in cardiovascular diseases. Studies have shown that miR-1 plays an important role in the regulation of cardiomyocyte apoptosis, which can be the result of oxidative stress. This study was designed to determine whether increased miR-1 levels lead to alterations in the expression of proteins related to oxidative stress, which could contribute to heart dysfunction. We compared cardiac function in wild-type (WT) and miR-1 transgene (miR-1/Tg) C57BL/6 mice (n ≥ 10/group). Echocardiography showed that stroke volume (SV), ejection fraction (EF), and fractional shortening (FS) were significantly decreased in miR-1/Tg mice. Concomitantly, the level of reactive oxygen species (ROS) was elevated in the cardiomyocytes from the miR-1/Tg mice, and activities of lactate dehydrogenase (LDH) and creatinine kinase (CK) in plasma were also increased in the miR-1/Tg mice. All of these changes could be reversed by LNA-anti-miR-1. In the cardiomyocytes of neonatal Wistar rats, overexpression of miR-1 exhibits higher ROS levels and lower resistance to H₂O₂-induced oxidative stress. We demonstrated that SOD1, Gclc, and G6PD are novel targets of miR-1 for post-transcriptional repression. MicroRNA-1 post-transcriptionally represses the expression of SOD1, Gclc, and G6PD, which is likely to contribute to the increased ROS level and the susceptibility to oxidative stress of the hearts of miR-1 transgenic mice.

Hyperlipidaemia is one of the major risk factors for atherosclerosis, coronary heart disease, stroke and diabetes. In the present study, we synthesized a new anthraquinone compound, 1,8-dihydroxy-3-succinic acid monoethyl ester-6-methylanthraquinone, and named it Kanglexin (KLX). The aim of this study was to evaluate whether KLX has a lipid-lowering effect and to explore the potential molecular mechanism. In this study, Sprague-Dawley rats were fed a high fat diet (HFD) for 5 weeks to establish a hyperlipidaemia model; then, the rats were orally administered KLX (20, 40, and 80 mg kg^-1·d^-1) or atorvastatin calcium (AT, 10 mg kg^-1·d^-1) once a day for 2 weeks. KLX had prominent effects on reducing blood lipids, hepatic lipid accumulation, body weight and the ratio of liver weight/body weight. Furthermore, KLXdramatically reduced the total cholesterol (TC) and triglyceride (TG) levels and lipid accumulation in a HepG2 cell model of dyslipidaemia induced by 1 mmol/L oleic acid (OA). KLX may decrease lipid levels by phosphorylating adenosine monophosphate-activated protein kinase (AMPK) and the downstream sterol regulatory element binding protein 2 (SREBP-2)/proprotein convertase subtilisin/kexin type 9 (PCSK9)/low-density lipoprotein receptor (LDLR) signalling pathway in the HFD rats and OA-treated HepG2 cells. The effects of KLX on the AMPK/SREBP-2/PCSK9/LDLR signalling pathway were abolished when AMPK was inhibited by compound C (a specific AMPK inhibitor) in HepG2 cells. In summary, KLX has an efficient lipid-lowering effect mediated by activation of the AMPK/SREBP-2/PCSK9/LDLR signalling pathway. Our findings may provide new insight into and evidence for the discovery of a new lipid-lowering drug for the prevention and treatment of hyperlipidaemia, fatty liver, and cardiovascular disease in the clinic.

Diabetic foot is one of the main causes of non-traumatic amputation. However, there is still lack of effective drugs to treat diabetic foot in clinical practice. Kanglexin (KLX) is a new anthraquinone compound with cardiovascular protective effects. Here we report that KLX accelerates diabetic wound healing by promoting angiogenesis via FGFR1/ERK signaling. Firstly, KM mice were injected (ip) with streptozocin to establish type 1 diabetic model. The full thickness wound with the diameter of 5 mm was prepared on the back of each mice. The wounds were treated with KLX once a day for 14 consecutive days. Results showed that KLX significantly accelerated the closure of diabetic wounds. Pathological studies of skin tissues around the wounds showed that KLX promoted the formation of granulation tissue and new blood vessels, increased collagen deposition and reduced inflammatory cell infiltration. Besides, KLX significantly alleviated advanced glycation end products (AGEs) - induced abnormal proliferation, migration and tubule formation of human umbilical vein endothelial cells (HUVECs), and up-regulated phospho-ERK1/2 both in the diabetic wound tissue and AGEs - treated HUVECs. Moreover, molecular docking results indicated that KLX had the potential to bind with FGF receptor 1 (FGFR1), and subsequent experiments confirmed that FGFR1 inhibitor PD173074 reversed the effect of KLX on promoting the phosphorylation of ERK1/2 and angiogenesis, suggesting that KLX promoted angiogenesis through FGFR1/ERK signaling. In conclusion, our study provides a new effective compound for treating diabetic wounds. More importantly, KLX has the potential to be developed as a topical drug to promote diabetic wound healing.

Background: Anthocyanins are a type of flavonoids that are natural water soluble glycosidic pigments with efficacious anti-cancer effects, which have good biological activity against many cancers including colorectal cancer (CRC). However, the exact molecular mechanism used by anthocyanins against cancer is unclear; it is also unclear what a reasonable dosage might be for their use against colorectal cancer. Methods: Western blotting, immunohistochemistry, MTT assay, xenograft model, and hematoxylin-eosin (HE) staining were used to perform the experiments. Results: Compared with the control group, anthocyanins could significantly inhibit the cell viability and proliferation and promote the apoptosis of human colon cancer HT29 cells. Furthermore, anthocyanins reduced tumor weight and volume in a colon tumor mouse model and downregulated the expression of PI3K protein, inhibited AKT expression and phosphorylation, decreased the Bcl-2 and Bax ratio and reduced survivin protein expression in the tumor tissue. Conclusion: Anthocyanins promoted apoptosis of CRC cells and inhibited colon cancer growth of xenografted tumors. Mechanistically, anthocyanins enhanced the Bcl-2/Bax and caspase-dependent apoptotic pathways through targeting the PI3K/AKT/survivin pathway, resulting in impairment of growth of CRC.

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