Adipose-derived stem cell exosome NFIC improves diabetic foot ulcers by regulating miR-204-3p/HIPK2

Abstract Background Diabetic foot ulcers (DFU) are a serious complication of diabetes that lead to significant morbidity and mortality. Recent studies reported that exosomes secreted by human adipose tissue-derived mesenchymal stem cells (ADSCs) might alleviate DFU development. However, the molecular mechanism of ADSCs-derived exosomes in DFU is far from being addressed. Methods Human umbilical vein endothelial cells (HUVECs) were induced by high-glucose (HG), which were treated with exosomes derived from nuclear factor I/C (NFIC)-modified ADSCs. MicroRNA-204-3p (miR-204-3p), homeodomain-interacting protein kinase 2 (HIPK2), and NFIC were determined using real-time quantitative polymerase chain reaction. Cell proliferation, apoptosis, migration, and angiogenesis were assessed using cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, wound healing, and tube formation assays. Binding between miR-204-3p and NFIC or HIPK2 was predicted using bioinformatics tools and validated using a dual-luciferase reporter assay. HIPK2, NFIC, CD81, and CD63 protein levels were measured using western blot. Exosomes were identified by a transmission electron microscope and nanoparticle tracking analysis. Results miR-204-3p and NFIC were reduced, and HIPK2 was enhanced in DFU patients and HG-treated HUVECs. miR-204-3p overexpression might abolish HG-mediated HUVEC proliferation, apoptosis, migration, and angiogenesis in vitro. Furthermore, HIPK2 acted as a target of miR-204-3p. Meanwhile, NFIC was an upstream transcription factor that might bind to the miR-204-3p promoter and improve its expression. NFIC-exosome from ADSCs might regulate HG-triggered HUVEC injury through miR-204-3p-dependent inhibition of HIPK2. Conclusion Exosomal NFIC silencing-loaded ADSC sheet modulates miR-204-3p/HIPK2 axis to suppress HG-induced HUVEC proliferation, migration, and angiogenesis, providing a stem cell-based treatment strategy for DFU

Application of 3D Printing-Assisted Articulating Spacer in Two-Stage Revision Surgery for Periprosthetic Infection after Total Knee Arthroplasty: A Retrospective Observational Study

Background. Bone cement spacers are widely used in two-stage revision surgeries for periprosthetic joint infection (PJI) after total knee arthroplasty. Current spacer design results in insufficient release of drugs; therefore, current spacers have low efficacy. In this study, we explored a set of alternative articular spacer using 3D printing technology. This novel spacer will increase effectiveness of revision surgery for PJI. Methods. The spacer was designed using CAD software and constructed on site using 3D-printed silicone mold during debridement surgery. We carried out a retrospective study among patients undergoing treatment using traditional static and new articular spacers. Infection control rate, bone loss, difficulty of revision surgery, knee joint range of motion, function evaluation, and subjective satisfaction of the patients in the two groups were compared. Results. Forty-two patients undergoing knee revision surgery between Jan 2014 and Nov 2019 were included in this study. Twenty-two patients were treated with static antibiotic cement spacers, whereas the other twenty patients were with treated with 3D printing-assisted antibiotic loaded articulating spacers. Patients in the articular group showed significantly lower bone loss on the femur site and tibial site compared with patients in the static group. In addition, patients in the articular group showed significantly less operation time, intraoperative blood loss, and improved knee function and patient overall satisfaction compared with patients in the static group. Conclusions. The 3D printing-assisted articular spacer provides satisfactory range of motion during the interim period, prevents bone loss, facilitates second-stage reimplantation and postoperative rehabilitation, and results in low reinfection and complication rates

Repetitive DNA sequence detection and its role in the human genome

Abstract Repetitive DNA sequences playing critical roles in driving evolution, inducing variation, and regulating gene expression. In this review, we summarized the definition, arrangement, and structural characteristics of repeats. Besides, we introduced diverse biological functions of repeats and reviewed existing methods for automatic repeat detection, classification, and masking. Finally, we analyzed the type, structure, and regulation of repeats in the human genome and their role in the induction of complex diseases. We believe that this review will facilitate a comprehensive understanding of repeats and provide guidance for repeat annotation and in-depth exploration of its association with human diseases