Patients with diabetes have severe vascular complications, such as diabetic nephropathy, diabetic retinopathy, cardiovascular disease, and neuropathy. Devastating vascular complications lead to increased mortality, blindness, kidney failure, and decreased overall quality of life in people with type 2 diabetes (T2D). Glycolipid metabolism disorder plays a vital role in the vascular complications of T2D. However, the specific mechanism of action remains to be elucidated. In T2D patients, vascular damage begins to develop before insulin resistance and clinical diagnosis. Endothelial dysregulation is a significant cause of vascular complications and the early event of vascular injury. Hyperglycemia and hyperlipidemia can trigger inflammation and oxidative stress, which impair endothelial function. Furthermore, during the pathogenesis of T2D, epigenetic modifications are aberrant and activate various biological processes, resulting in endothelial dysregulation. In the present review, we provide an overview and discussion of the roles of hyperglycemia- and hyperlipidemia-induced endothelial dysfunction, inflammatory response, oxidative stress, and epigenetic modification in the pathogenesis of T2D. Understanding the connections of glucotoxicity and lipotoxicity with vascular injury may reveal a novel potential therapeutic target for diabetic vascular complications.

In the history of nucleic acid research, DNA has always been the main research focus. After the sketch of the human genome was completed in 2000, RNA has been started to gain more attention due to its abundancies in the cell and its essential role in cellular physiology and pathologies. Recent studies have shown that RNAs are susceptible to oxidative damage and oxidized RNA is able to break the RNA strand, and affect the protein synthesis, which can lead to cell degradation and cell death. Studies have shown that RNA oxidation is one of the early events in the formation and development of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. However, its molecular mechanism, as well as its impact on these diseases, are still unclear. In this article, we review the different types of RNA oxidative damage and the neurodegenerative diseases that are reported to be associated with RNA oxidative damage. In addition, we discuss recent findings on the association between RNA oxidative damage and the development of neurodegenerative diseases, which will have great significance for the development of novel strategies for the prevention and treatment of these diseases.

Doxorubicin (DOX)-induced cardiotoxicity has been one of the major limitations for its clinical use. Although extensive studies have been conducted to decipher the molecular mechanisms underlying DOX cardiotoxicity, no effective preventive or therapeutic measures have yet been identified. Microarray analysis showed that multiple long non-coding RNAs (lncRNAs) are differentially expressed between control- and DOX-treated cardiomyocytes. Functional enrichment analysis indicated that the differentially expressed genes are annotated to cardiac hypertrophic pathways. Among differentially expressed lncRNAs, cardiomyocyte mitochondrial dynamic-related lncRNA 1 (CMDL-1) is the most significantly downregulated lncRNA in cardiomyocytes after DOX exposure. The protein-RNA interaction analysis showed that CMDL-1 may target dynamin-related protein 1 (Drp1). Mechanistic analysis shows that lentiviral overexpression of CMDL-1 prevents DOX-induced mitochondrial fission and apoptosis in cardiomyocytes. However, overexpression of CMDL-1 cannot effectively reduce mitochondrial fission when Drp1 is minimally expressed by small interfering RNA Drp1 (siDrp1). Overexpression of CMDL-1 promotes the association between CMDL-1 and Drp1, as well as with phosphorylated (p-)Drp1, as evidenced by RNA immunoprecipitation analysis. These data indicate the role of CMDL-1 in posttranslational modification of a target protein via regulating its phosphorylation. Collectively, our data indicate that CMDL-1 may play an anti-apoptotic role in DOX cardiotoxicity by regulating Drp1 S637 phosphorylation. Thus, CMDL-1 may serve as a potential therapeutic target in DOX cardiotoxicity.

Excessive production of free radicals can induce cellular damage, which is associated with many diseases. RNA is more susceptible to oxidative damage than DNA due to its single-stranded structure, and lack of protective proteins. Yet, oxidative damage to RNAs received little attention. Accumulating evidence reveals that oxidized RNAs may be dysfunctional and play fundamental role in the occurrence and development of type 2 diabetes (T2D) and its complications. Oxidized guanine nucleoside, 8-oxo-7, 8-dihydroguanine (8-oxoGuo) is a biomarker of RNA oxidation that could be associated with prognosis in patients with T2D. Nowadays, some clinical trials used antioxidants for the treatment of T2D, though the pharmacological effects remained unclear. In this review, we overview the cellular handling mechanisms and the consequences of the oxidative RNA damage for the better understanding of pathogenesis of T2D and may provide new insights to better therapeutic strategy.

High expression of SETDB1 mediated by miR-29a-3p associates with poor prognosis and immune invasion in breast invasive carcinoma Xiatian Chen, Xin Li, Chuang Wei, Cheng Zhao, Shaoying Wang, Jinning Gao