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               ·198 ·                            南 京    医 科 大 学 学         报                        2026年2月


              A                                  B hAMSC⁃exo⁃F hAMSC⁃exo⁃M
                                                                  Group
                     hAMSC⁃exo⁃F vs.hAMSC⁃exo⁃M                   hsa⁃miR⁃335⁃3p  1.5
                                                                       1
                                                                  hsa⁃miR⁃301a⁃3p  1.Glycerophospholipid metabolism
                                 hsa⁃miR⁃367⁃3p                        0.5
                          hsa⁃miR⁃1268b
                                                                  hsa⁃miR⁃664a⁃5p  Glycosaminoglycan biosynthesis
                                                                       0
                          hsa⁃miR⁃149⁃5p
                                                                  hsa⁃miR⁃34a⁃5p ⁃0.5
                                       hsa⁃miR⁃1291                       Arachidonic acid metabolism
                                  hsa⁃miR⁃218⁃5p
                 3                                                hsa⁃miR⁃218⁃5p ⁃1
                                 hsa⁃miR⁃29b⁃3p                   hsa⁃miR⁃29a⁃3p ⁃1.5  C  hAMSC⁃exo⁃F
                            hsa⁃miR⁃708⁃5p
                                                                  hsa⁃miR⁃1291
                                                                  hsa⁃miR⁃136⁃3p
                          hsa⁃miR⁃486⁃5p
               P  2                         Up                    hsa⁃miR⁃4454
               -lg        hsa⁃miR⁃328⁃3p  hsa⁃miR⁃34a⁃5p  Down    hsa⁃miR⁃486⁃5p
                                      hsa⁃miR⁃664a⁃5p  Normal
                                                                  hsa⁃miR⁃584⁃5p
                                                                                        71       337     50
                                                                  hsa⁃miR⁃671⁃5p
                 1
                                                                  hsa⁃miR⁃92a⁃3p
                                                                  hsa⁃miR⁃328⁃3p
                                                                  hsa⁃miR⁃1268a
                                                                  hsa⁃miR⁃1268b
                 0                                                       2.ECM⁃receptor interaction
                                                                  hsa⁃miR⁃193b⁃5p                 hAMSC⁃exo⁃M
                  -5.0   -2.5   0     2.5                         hsa⁃miR⁃149⁃5p  Focal adhesion
                             log2 FC                              hsa⁃miR⁃362⁃5p  Glutamatergic synapse
                                                                  hsa⁃miR⁃708⁃5p
                                                                          Pathways in cancer
                                                                  hsa⁃miR⁃1287⁃5p
                                                                          Inflammatory mediator regula⁃
                                                                  hsa⁃miR⁃377⁃3p
                                                                  hsa⁃miR⁃2682⁃3p  tion of TRP channels
                                                                  hsa⁃miR⁃484
                                                                  hsa⁃miR⁃3182
                                                                  hsa⁃miR⁃3615
              D 0         2         4         6         8          E  0         2         4         6         8
                 Pathways in cancer                                   cAMP signaling pathway
                 Adrenergic signaling in cardiac myocytes             Focal adhesion
                 Focal adhesion                                       Proteoglycans in cancer
                 Proteoglycans in cancer                              Endocytosis
                 MAPK signaling pathway                               Insulin secretion
               hAMSC⁃exo⁃F unique  Estrogen signaling pathway        hAMSC⁃exo⁃M unique  Rap1 signaling pathway
                                                                      Cholinergic synapse
                 Rap1 signaling pathway
                                                                      Circadian entrainment
                 Insulin secretion
                                                                      Adrenergic signaling in cardiomyocytes
                 cGMP⁃PKG signaling pathway
                 Small cell lung cancer
                                                                      ECM⁃receptor interaction
                 Wnt signaling pathway
                                                                      Glycerophospholipid metabolism
                 Signaling pathways regulating pluripotency of stem cells
                                                                      Non⁃small cell lung cancer
                                                                      Neurotrophin signaling pathway
                 Pl3K⁃Akt signaling pathway
                 ECM⁃receptor interaction
                                                                      Choline metabolism in cancer
                 Hedgehog signaling pathway
                                                                      HIF⁃1 signaling pathway
                 Oxytocin signaling pathway                           Pathways in cancer
                 cAMP signaling pathway                               Melanogenesis
                 Axon guidance                                        Basal cell carcinoma
                 VEGF signating pathway                               MAPK signaling pathway
                 Toxoplasmosis                                        Wnt signaling pathway
                0         2         4         6         8             0         2         4         6         8
                                    -lg P                                                -lg P
              F
                0         2         4         6         8
                 Dilated cardiomyopathy
                 Estrogen signaling pathway
                 Pathways in cancer
                 Focal adhesion
                 Endocytosis
                 Platelet activation
                 ECM⁃receptor interaction
                 Rap1 signaling pathway
               Common  Melanogensis
                 Thyroid hormone signaling pathway
                 Axon guidance
                 Arrhythmogenic right ventricular cardiomyopathy(ARVC)
                 Calclum signaling pathway
                 Proteoglycans in cancer
                 Non⁃small cell lung cancer
                 Basal cell carcinoma
                 Signaling pathways regulating pluripotency of stem cells
                 Adrenergic signaling in eardiomyocytes
                 TypeⅡdiabetes mellitus
                 Hedgehog signaling pathway
                0         2         4         6         8
                                    -lg P
                 A:Volcano diagrams of differentially expressed miRNAs in hAMSC⁃exo⁃F vs. hAMSC⁃exo⁃M. B:Heatmap of the levels of differentially expressed
              miRNAs in hAMSC⁃exo⁃F and hAMSC⁃exo⁃M. The significantly enriched pathways are shown on the right. C:Venn diagram of pairwise analysis of
              hAMSC⁃exo⁃Fvs.hAMSC⁃exo⁃M.D,E:KEGGanalysisofuniquemiRNAsofhAMSC⁃exo⁃F(D)andhAMSC⁃exo⁃M(E)whenperformedtheirpairwiseanalysis.
              F:KEGG analysis of common miRNAs in hAMSC⁃exo⁃F and hAMSC⁃exo⁃M. The red bar represents the ⁃lg P and the black dot represents gene ratio
             (defined as the proportion of genes annotated in this specific pathway term relative to the total number of genes in the pathway database).
                                           图7 男女株hAMSC⁃exo miRNA表达谱比较分析
                          Figure 7 Pairwise bioinformatics analysis of miRNA profiles in male and female hAMSC⁃exo
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