Objective:To investigate the effect of exosomes from lung cancer cells on the ability of lung cancer metastasis in-duced by M2 macrophages.Methods:The exosomes secreted by 16HBE,A549 and H522(16HBE exo,A549 exo,H522 exo)were extracted and identified.M0 macrophages co-incubated with 10 μg/ml 16HBE exo,A549 exo,H522 exo,PBS(16HBE exo group,A549 exo group,H522 exo group,PBS group),the expressions of Arginase-1,CD206,CD163,TGF-β,iNOS,and IL-1β in macro-phages in each group were detected by qRT-PCR,the proportion of CD206+CD163+macrophages was detected by flow cytometry,the phosphorylation levels of ERK1/2 and STAT3 in macrophages were detected by Western blot.A549 and H522 cells were co-incubated with macrophages in the above groups(16HBE exo+M0 group,A549 exo+M0 group,H522 exo+M0 group,PBS+M0 group),and the migration and invasive ability of A549 and H522 cells in each group were detected by Transwell chamber method.Results:Compared with PBS group,the expressions of Arginase-1,CD206,CD163 and TGF-β in macrophages in A549 exo group and H522 exo group were significantly up-regulated(P<0.001),and the expressions of iNOS and IL-1β were significantly down-regulated(P<0.001).The proportion of CD206+CD163+macrophages was increased significantly(P<0.001),and the phosphorylation levels of ERK1/2 and STAT3 were increased significantly(P<0.001).There was no significant difference in the above indicators between the 16HBE exo group and the PBS group(P>0.05).The migration ablility and invasion ablility of A549 and H522 cells in A549 exo+M0 group and H522 exo+M0 group were significantly increased(P<0.001).Conclusion:Lung cancer cell exosomes can induce the polarization of M2 macrophages by activating the ERK1/2/STAT3 signaling pathway to promote tumor migration and invasion.

Objective:To investigate the effect of exosomes from lung cancer cells on the ability of lung cancer metastasis in-duced by M2 macrophages.Methods:The exosomes secreted by 16HBE,A549 and H522(16HBE exo,A549 exo,H522 exo)were extracted and identified.M0 macrophages co-incubated with 10 μg/ml 16HBE exo,A549 exo,H522 exo,PBS(16HBE exo group,A549 exo group,H522 exo group,PBS group),the expressions of Arginase-1,CD206,CD163,TGF-β,iNOS,and IL-1β in macro-phages in each group were detected by qRT-PCR,the proportion of CD206+CD163+macrophages was detected by flow cytometry,the phosphorylation levels of ERK1/2 and STAT3 in macrophages were detected by Western blot.A549 and H522 cells were co-incubated with macrophages in the above groups(16HBE exo+M0 group,A549 exo+M0 group,H522 exo+M0 group,PBS+M0 group),and the migration and invasive ability of A549 and H522 cells in each group were detected by Transwell chamber method.Results:Compared with PBS group,the expressions of Arginase-1,CD206,CD163 and TGF-β in macrophages in A549 exo group and H522 exo group were significantly up-regulated(P<0.001),and the expressions of iNOS and IL-1β were significantly down-regulated(P<0.001).The proportion of CD206+CD163+macrophages was increased significantly(P<0.001),and the phosphorylation levels of ERK1/2 and STAT3 were increased significantly(P<0.001).There was no significant difference in the above indicators between the 16HBE exo group and the PBS group(P>0.05).The migration ablility and invasion ablility of A549 and H522 cells in A549 exo+M0 group and H522 exo+M0 group were significantly increased(P<0.001).Conclusion:Lung cancer cell exosomes can induce the polarization of M2 macrophages by activating the ERK1/2/STAT3 signaling pathway to promote tumor migration and invasion.

BACKGROUND:Observational studies have suggested that statin drugs may have a protective effect on bone density,making them a potential treatment option for osteoporosis. OBJECTIVE:To evaluate the causal relationship between drug target-mediated lipid phenotypes and bone mineral density(BMD)using Mendelian randomization methods. METHODS:We obtained single nucleotide polymorphismsrelated to statin drugs and BMD data from the IEU Open GWAS database.The primary analysis method was the inverse variance weighted method,and we also used weighted median,simple median,weighted mode,and MR-Egger regression.We usedβ values and 95%confidence intervals(CI)to assess the causal relationship between statin drugs and BMD.Additionally,we conducted sensitivity analyses to validate the results,assessed heterogeneity using Cochran's Q test,examined for horizontal pleiotropy using the MR-Egger intercept test,and performed leave-one-out analyses to determine if individual or multiplesingle nucleotide polymorphism influenced the results. RESULTS AND CONCLUSION:There was a significant association between the statin target of action,3-hydroxy-3-methyl glutaryl coenzyme A reductase-mediated low-density lipoprotein cholesterol,and heel bone BMD(β=-0.086,95%CI:-0.117 to-0.055,P=5.42×10-8)and whole-body BMD(β=-0.193,95%CI:-0.288 to-0.098,P=7.35×10-5).The findings of this study support the protective effect of statin drugs on BMD.These findings not only deepen our understanding of the relationship between cholesterol-related genes and bone health but also reveal potential therapeutic targets for improving BMD.

BACKGROUND:Epidemiologic studies have shown a correlation between type 2 diabetes mellitus and bone mineral density,but the causal association between the two and whether it is age-related remains unknown. OBJECTIVE:To study the correlation between type 2 diabetes mellitus and whole body bone mineral density at unspecified age and at all ages based on the Mendelian randomization technique. METHODS:The genome-wide association study(GWAS)data of type 2 diabetes mellitus and bone mineral density at all ages were selected from the IEU GWAS database of the University of Bristol.The exposure data were single nucleotide polymorphisms with significant correlation with type 2 diabetes mellitus as instrumental variables,and bone mineral density at all ages was selected as the outcome variable.Two-sample Mendelian randomization analysis of type 2 diabetes mellitus and bone mineral density was performed using inverse variance weighted method,weighted median estimator,and MR-Egger regression.The βvalue was used to evaluate the causal relationship between type 2 diabetes mellitus and bone mineral density at all ages. RESULTS AND CONCLUSION:A total of 118 single nucleotide polymorphisms were extracted from the GWAS summary data as instrumental variables.The MR-Egger regression results showed that there was no horizontal pleiotropy,but there was heterogeneity.Therefore,this study was based on the inverse variance weighted results.Inverse variance weighted results showed that type 2 diabetes mellitus may be a potential protective factor for bone mineral density and is associated with age:age-unspecified bone mineral density[β=0.038,95%confidence interval(CI):1.01-1.07,P=0.002],bone mineral density over 60 years old(β=0.052,95%CI:1.01-1.09,P=0.027),bone mineral density between 45-60 years old(β=0.049,95%CI:1.01-1.09,P=0.009),bone mineral density between 30-45 years old(β=0.033,95%CI:0.99-1.07,P=0.127).bone mineral density of 15-30 years old(β=0.025,95%CI:0.95-1.10,P=0.506),bone mineral density of 0-15 years old(β=0.006,95%CI:0.96-1.04,P=0.716).Similar results were obtained from the MR-Egger regression and weighted median estimator analyses.These findings indicate that type 2 diabetes mellitus may be one of the protective factors of bone mineral density,and there is a correlation with age.