Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts.

BACKGROUND: Fibroblast plays a major role in tendon-bone healing. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) can activate fibroblasts and promote tendon-bone healing via the contained microRNAs (miRNAs). However, the underlying mechanism is not comprehensively understood. Herein, this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets, and to verify their effects as well as mechanisms on fibroblasts. AIM: To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts. METHODS: BMSC-derived exosomal miRNAs data (GSE71241, GSE153752, and GSE85341) were downloaded from the Gene Expression Omnibus (GEO) database. The candidate miRNAs were obtained by the intersection of three data sets. TargetScan was used to predict potential target genes for the candidate miRNAs. Functional and pathway analyses were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, by processing data with the Metascape. Highly interconnected genes in the protein-protein interaction (PPI) network were analyzed using Cytoscape software. Bromodeoxyuridine, wound healing assay, collagen contraction assay and the expression of COL I and α-smooth muscle actin positive were applied to investigate the cell proliferation, migration and collagen synthesis. Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic, tenogenic, and chondrogenic potential. RESULTS: Bioinformatics analyses found two BMSC-derived exosomal miRNAs, has-miR-144-3p and has-miR-23b-3p, were overlapped in three GSE datasets. PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog (PTEN). In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation, migration and collagen synthesis of NIH3T3 fibroblasts. Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts. Inhibition of PTEN also promoted the fibroblastic, tenogenic, and chondrogenic potential of NIH3T3 fibroblasts. CONCLUSION: BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways, which may serve as potential targets to further promote tendon-bone healing.

Comment on "Outcomes of different minimally invasive surgical treatments for vertebral compression fractures: An observational study".

Recently we read the article entitled "Outcomes of different minimally invasive surgical treatments for vertebral compression fractures: An observational study". This was an observational study that reviewed the safety and efficacy of different cement augmentation modalities for vertebral compression fractures under osteoporotic condition. Overall, this is a valuable study that can provide a reference for clinical practice. On the other hand, we also noticed some points in the article and are willing to share our views. Further studies with a higher level of evidence can add more knowledge regarding relevant concerns.

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation.

BACKGROUND: Acute muscle injuries are one of the most common injuries in sports. Severely injured muscles are prone to re-injury due to fibrotic scar formation caused by prolonged inflammation. How to regulate inflammation and suppress fibrosis is the focus of promoting muscle healing. Recent studies have found that myoblasts and macrophages play important roles in the inflammatory phase following muscle injury; however, the crosstalk between these two types of cells in the inflammatory environment, particularly the exosome-related mechanisms, had not been well studied. AIM: To evaluate the effects of exosomes from inflammatory C2C12 myoblasts (IF-C2C12-Exos) on macrophage polarization and myoblast proliferation/differentiation. METHODS: A model of inflammation was established in vitro by lipopolysaccharide stimulation of myoblasts. C2C12-Exos were isolated and purified from the supernatant of myoblasts by gradient centrifugation. Multiple methods were used to identify the exosomes. Gradient concentrations of IF-C2C12-Exos were added to normal macrophages and myoblasts. PKH67 fluorescence tracing was used to identify the interaction between exosomes and cells. Microscopic morphology, Giemsa stain, and immunofluorescence were carried out for histological analysis. Additionally, ELISA assays, flow cytometry, and western blot were conducted to analyze molecular changes. Moreover, myogenic proliferation was assessed by the BrdU test, scratch assay, and CCK-8 assay. RESULTS: We found that the PKH-67-marked C2C12-Exos can be endocytosed by both macrophages and myoblasts. IF-C2C12-Exos induced M1 macrophage polarization and suppressed the M2 phenotype in vitro. In addition, these exosomes also stimulated the inflammatory reactions of macrophages. Furthermore, we demonstrated that IF-C2C12-Exos disrupted the balance of myoblast proliferation/differentiation, leading to enhanced proliferation and suppressed fibrogenic/myogenic differentiation. CONCLUSION: IF-C2C12-Exos can induce M1 polarization, resulting in a sustained and aggravated inflammatory environment that impairs myoblast differentiation, and leads to enhanced myogenic proliferation. These results demonstrate why prolonged inflammation occurs after acute muscle injury and provide a new target for the regulation of muscle regeneration.

Relationship between hospital or surgeon volume and outcomes in joint arthroplasty: protocol for a suite of systematic reviews and dose-response meta-analyses.

INTRODUCTION: Joint arthroplasty is a particularly complex orthopaedic surgical procedure performed on joints, including the hip, knee, shoulder, ankle, elbow, wrist and even digit joints. Increasing evidence from volume-outcomes research supports the finding that patients undergoing joint arthroplasty in high-volume hospitals or by high-volume surgeons achieve better outcomes, and minimum case load requirements have been established in some areas. However, the relationships between hospital/surgeon volume and outcomes in patients undergoing arthroplasty are not fully understood. Furthermore, whether elective arthroplasty should be restricted to high-volume hospitals or surgeons remains in dispute, and little is known regarding where the thresholds should be set for different types of joint arthroplasties. METHODS AND ANALYSES: This is a protocol for a suite of systematic reviews and dose-response meta-analyses, which will be amended and updated in conjunction with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Electronic databases, including PubMed and Embase, will be searched for observational studies examining the relationship between the hospital or surgeon volume and clinical outcomes in adult patients undergoing primary or revision of joint arthroplasty. We will use records management software for study selection and a predefined standardised file for data extraction and management. Quality will be assessed using the Newcastle-Ottawa Scale, and the meta-analysis, subgroup analysis and sensitivity analysis will be performed using Stata statistical software. Once the volume-outcome relationships are established, we will examine the potential non-linear relationships between hospital/surgeon volume and outcomes and detect whether thresholds or turning points exist. ETHICS AND DISSEMINATION: Ethical approval is not required, because these studies are based on aggregated published data. The results of this suite of systematic reviews and meta-analyses will be submitted to peer-reviewed journals for publication. PROSPERO REGISTRATION NUMBER: CRD42017056639.

Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials.

This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection (SSI) after colorectal surgery. Fourteen trials involving 1524 participants were included. Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy. Current evidence suggested that probiotics in combination with antibiotics could be recommended.