Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

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 andα-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 hasmiR-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.

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(IFC2C12-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.Further-more,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.

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.