Diabetic vascular complications can affect both microvascular and macrovascular. Diabetic microvascular complications, such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and diabetic cardiomyopathy, are believed to be caused by oxidative stress. The Nox family of NADPH oxidases is a significant source of reactive oxygen species and plays a crucial role in regulating redox signaling, particularly in response to high glucose and diabetes mellitus. This review aims to provide an overview of the current knowledge about the role of Nox4 and its regulatory mechanisms in diabetic microangiopathies. Especially, the latest novel advances in the upregulation of Nox4 that aggravate various cell types within diabetic kidney disease will be highlighted. Interestingly, this review also presents the mechanisms by which Nox4 regulates diabetic microangiopathy from novel perspectives such as epigenetics. Besides, we emphasize Nox4 as a therapeutic target for treating microvascular complications of diabetes and summarize drugs, inhibitors, and dietary components targeting Nox4 as important therapeutic measures in preventing and treating diabetic microangiopathy. Additionally, this review also sums up the evidence related to Nox4 and diabetic macroangiopathy.

Extracellular vesicles (EVs) generated from mesenchymal stem cells (MSCs) play an essential role in modulating cell—cell communication and tissue regeneration. The clinical translation of EVs is constrained by the poor yield of EVs. Extrusion has recently become an effective technique for producing a large scale of nanovesicles (NVs). In this study, we systematically compared MSC NVs (from extrusion) and EVs (from natural secretion). Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs. Additionally, microRNAs in NVs are related to cardiac repair, fibrosis repression, and angiogenesis. Lastly, intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction.

Myocardial infarction (MI) is a devastating disease with high morbidity and mortality caused by the irreversible loss of functional cardiomyocytes and heart failure (HF) due to the restricted blood supply. Mesenchymal stem cells (MSCs) have been emerging as lead candidates to treat MI and subsequent HF mainly through secreting multitudinous factors of which exosomes act as the most effective constituent to boost the repair of heart function through carrying noncoding RNAs and proteins. Given the advantages of higher stability in the circulation, lower toxicity, and controllable transplantation dosage, exosomes have been described as a wonderful and promising cell-free treatment method in cardiovascular disease. Nowadays, MSC-derived exosomes have been proposed as a promising therapeutic approach to improve cardiac function and reverse heart remodeling. However, exosomes’ lack of modification cannot result in desired therapeutic effect. Hence, optimized exosomes can be developed via various engineering methods such as pharmacological compound preconditioned MSCs, genetically modified MSCs, or miRNA-loaded exosomes and peptide tagged exosomes to improve the targeting and therapeutic effects of exosomes. The biological characteristics, therapeutic potential, and optimizing strategy of exosomes will be described in our review.

Objectives. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. Methods. GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. Results. There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. Conclusions. We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.

Background: Diabetic cardiomyopathy (DCM) is one of the serious complications of the accumulated cardiovascular system in the long course of diabetes. To date, there is no effective treatment available for DCM. Circular RNA (circRNA) is a novel r2egulatory RNA that participates in a variety of cardiac pathological processes. However, the regulatory role of circular RNA MAP3K5 (circMAP3K5) in DCM is largely unclear.Methods and Results: Microarray analysis of DCM rats' heart circular RNAs was performed and the highly species‐conserved circRNA mitogen‐activated protein kinase kinase kinase 5 (circMAP3K5) was identified, which participates in DCM processes. High glucose‐provoked cardiotoxicity leads to the up‐regulation of circMAP3K5, which mechanistically contributes to cardiomyocyte cell death. Also, in high glucose‐induced H9c2 cardiomyocytes, the level of apoptosis was significantly increased, as well as the expression of circMAP3K5. In contrast, the depletion of circMAP3K5 could reduce high glucose‐induced apoptosis in cardiomyocytes. In terms of mechanism, circMAP3K5 acts as a miR‐22‐3p sponge and miR‐22‐3p directly target death‐associated protein kinase 2 (DAPK2) in H9c2 cardiomyocytes, where in circMAP3K5 upregulates DAPK2 expression by targeting miR‐22‐3p. Moreover, we also found that miR‐22‐3p inhibitor and pcDNA DAPK2 could antagonize the protective effects brought by the depletion of circMAP3K5.Conclusion: CircMAP3K5 is a highly conserved noncoding RNA that is upregulated during DCM process. We concluded that circMAP3K5 promotes high glucose‐induced cardiomyocyte apoptosis by regulating the miR‐22‐3p/DAPK2 axis. The results of this study highlight a novel and translationally important circMAP3K5‐based therapeutic approach for DCM.

Mental stress, a significant risk factor for coronary artery disease (CAD), has garnered widespread attention in recent years. Numerous studies indicate a close link between the development of CAD and mental stress. Mental stress can trigger acute coronary events and worsen CAD through vascular inflammation, endothelial dysfunction, coagulation cascade, and neuro-endocrine-immune response. In addition, a bidirectional link exists between mental stress and CAD, leading to a vicious cycle that further hinders recovery from the disease. Therefore, early detection, diagnosis, and intervention for mental stress, combined with mental stress management alongside standard CAD treatments are crucial to effectively breaking this vicious cycle. This narrative review examines the current state of research on the link between mental stress and CAD, examining how mental stress influences the onset, progression, and prognosis of CAD. It aims to emphasize the necessity of early identification and comprehensive management of mental stress to improve the patient outcomes and prevent disease progression. It also recommends psychocardiology therapy in treatment plans and proposes an innovative model for early screening, diagnosis, and intervention.