Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1β). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM.

Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.

With the increasing of altitude activities from low-altitude people, the study of high altitude cerebral edema (HACE) has been revived. HACE is a severe acute mountain sickness associated with exposure to hypobaric hypoxia at high altitude, often characterized by disturbance of consciousness and ataxia. As for the pathogenesis of HACE, previous studies suggested that it might be related to the disorder of cerebral blood flow, the destruction of blood-brain barrier and the injury of brain parenchyma cells caused by inflammatory factors. In recent years, studies have confirmed that the imbalance of REDOX homeostasis is also involved in the pathogenesis of HACE, which mainly leads to abnormal activation of microglia and destruction of tight junction of vascular endothelial cells through the excessive production of mitochondrial-related reactive oxygen species. Therefore, this review summarizes the role of REDOX homeostasis and the potential of the treatment of REDOX homeostasis in HACE, which is of great significance to expand the understanding of the pathogenesis of HACE. Moreover, it will also be helpful to further study the possible therapy of HACE related to the key link of REDOX homeostasis.

Cancer treatment is a significant challenge for the global health system, although various pharmacological and therapeutic discoveries have been made. It has been widely established that cancer is associated with epigenetic modification, which is reversible and becomes an attractive target for drug development. Adding chemical groups to the DNA backbone and modifying histone proteins impart distinct characteristics on chromatin architecture. This process is mediated by various enzymes modifying chromatin structures to achieve the diversity of epigenetic space and the intricacy in gene expression files. After decades of effort, epigenetic modification has represented the hallmarks of different cancer types, and the enzymes involved in this process have provided novel targets for antitumor therapy development. Epigenetic drugs show significant effects on both preclinical and clinical studies in which the target development and research offer a promising direction for cancer therapy. Here, we summarize the different types of epigenetic enzymes which target corresponding protein domains, emphasize DNA methylation, histone modifications, and microRNA-mediated cooperation with epigenetic modification, and highlight recent achievements in developing targets for epigenetic inhibitor therapy. This article reviews current anticancer small-molecule inhibitors targeting epigenetic modified enzymes and displays their performances in different stages of clinical trials. Future studies are further needed to address their off-target effects and cytotoxicity to improve their clinical translation.

The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 μg/mL to 3200 μg/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis.