cause of nontraumatic limb amputations, threatening patient health and quality of life. [1,2] Wound healing is a fascinatingly complex biological process. Traditionally, it is divided into four overlapping phases: hemostasis, inflammation, proliferation and remodeling. [3,4] Compared with the healing of other wounds, the healing of diabetic wounds gets stalled in the inflam matory phase, which is characterized by excessive production of reactive oxygen species (ROS), proinflammatory cytokines and proteases. [5,6] Excessive ROS produc tion cause irreversible oxidative damage to biomacromolecules (such as lipids, nucleic acids, and proteins) and the cells within the wound (such as endothelial cells, keratino cytes, and fibroblasts). This inhibits angiogenesis, granulation tissue forma tion, and wound healing. [7,8] The endo genous antioxidant system is inadequate to remove excessive ROS, and the use of exogenous antioxidants is recommended to prevent oxidative stress damage. With the rapid advancements in nanomedicine, numerous antioxidative nanomaterialsincluding melanin nanoparticles (NPs), metalbased nanomaterials (Au, Ag, Pt NPs), metal oxidebased nanomaterials (CeO 2 , Fe 3 O 4 , TiO 2 , alumina, SiO 2 ), [9,10] and quantum dots-are being used in wound dressing systems to scavenge excess ROS. [11] In addition to oxidative damage, bacterial infections also hinder diabetic wound healing. [12,13] Diabetic wounds are more prone to bacterial infection owing to impaired immune responses, and bacterial infections cause increased ROS pro duction and worsen the inflammatory response in wounds. [14,15] Bacteria easily acquire multidrug resistance owing to antibi otic misuse. Therefore, among various available antimicrobial therapies, photothermal therapy (PTT) has been attracting widespread attention. [16] In PTT, nearinfrared (NIR) laser irra diation is used to induce a local increase in temperature, which can damage bacterial cell membranes and denature bacterial proteins, thus causing bactericidal effects. [16,17] So far, a variety of nanomaterialbased photothermal agents have been incorpo rated into wound dressings to treat bacteriainfected wounds. [17] However, monotherapy with PTT may lead to additional local ROS production, thus delaying wound healing. Therefore, anThe treatment of diabetic wounds remains challenging due to the excess levels of oxidative stress, vulnerability to bacterial infection, and persistent inflammation response during healing. The development of hydrogel wound dressings with ideal anti-inflammation, antioxidant, and anti-infective properties is an urgent clinical requirement. In the present study, an injectable thermosensitive niobium carbide (Nb 2 C)-based hydrogel (Nb 2 C@Gel) with antioxidative and antimicrobial activity is developed to promote diabetic wound healing. The Nb 2 C@Gel system is composed of Nb 2 C and a PLGA-PEG-PLGA triblock copolymer. The fabricated Nb 2 C nanosheets (NSs) show good biocompatibility during in vitro cytotoxicity and hemocompatibility assays and in vivo t...
Background Mesenchymal stem cells including adipose-derived stem cells (ASCs) have a considerable potential in the field of translational medicine. Unfortunately, multiple factors (e.g., older age, co-existing diabetes, and obesity) may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs—including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)—have been shown to play important roles in stem cell biology. However, the overall diabetes-related and aging-related expression patterns and interactions of these RNAs in ASCs remain unknown. Method The phenotypes and functions of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donors were evaluated by in vitro assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to identify the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences among groups. The lncRNA- or circRNA-associated competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into O-ASCs and verified by PCR. Results ASCs from diabetic and old donors showed inferior migration ability and increased cellular senescence. Furthermore, O-ASCs have decreased capacities for promoting endothelial cell angiogenesis and fibroblast migration, compared with Y-ASCs. The DE miRNAs, mRNAs, lncRNAs, and circRNAs were successfully identified by RNA-seq in O-ASCs vs. Y-ASCs and D-ASCs vs. O-ASCs. GO and KEGG analyses demonstrated that DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks revealed critical DE mRNAs in the above groups. RNAs with high fold changes and low p values were validated by PCR. ceRNA networks were constructed based on bioinformatics analyses and validated RNAs. Additionally, the lncRNA RAET1E-AS1–miR-145-5p–WNT11/BMPER axis was validated by PCR and correlation analyses. Finally, the overexpression of miR-145-5p was found to rejuvenate O-ASCs phenotype and augment the functionality of these cells. Conclusion Our research may provide insights regarding the underlying mechanisms of ASC dysfunction; it may also offer novel targets for restoring therapeutic properties in ASCs.
Background: Diabetes mellitus is a worldwide disease with high incidence. Diabetic peripheral neuropathy (DPN) is one of the most common but often ignored complications of diabetes mellitus that cause numbness and pain, even paralysis. Recent studies demonstrate that Schwann cells (SCs) in the peripheral nervous system play an essential role in the pathogenesis of DPN. Furthermore, various transcriptome analyses constructed by RNA-seq or microarray have provided a comprehensive understanding of molecular mechanisms and regulatory interaction networks involved in many diseases. However, the detailed mechanisms and competing endogenous RNA (ceRNA) network of SCs in DPN remain largely unknown.Methods: Whole-transcriptome sequencing technology was applied to systematically analyze the differentially expressed mRNAs, lncRNAs and miRNAs in SCs from DPN rats and control rats. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the differentially expressed genes. Following this, lncRNA-mRNA co-expression network and ceRNA regulatory network were constructed by bioinformatics analysis methods. Results:The results showed that 2925 mRNAs, 164 lncRNAs and 49 miRNAs were significantly differently expressed in SCs from DPN rats compared with control rats. 13 mRNAs, 7 lncRNAs and 7 miRNAs were validated by qRT-PCR and consistent with the RNA-seq data. Functional and pathway analyses revealed that many enriched biological processes of GO terms and pathways were highly correlated with the function of SCs and the pathogenesis of DPN. Furthermore, a global lncRNA-miRNA-mRNA ceRNA regulatory network in DPN model was constructed and miR-212-5p and the significantly correlated lncRNAs with high degree were identified as key mediators in the pathophysiological processes of SCs in DPN. These RNAs would contribute to the diagnosis and treatment of DPN.
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