Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.

High‐fat‐diet‐induced obesity promotes simultaneous progression of lung cancer and atherosclerosis in apolipoprotein E‐knockout mice

Background:Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co‐exist in the same individual.The present study aimed to investigate the role of high‐fat‐diet(HFD)‐induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E‐knockout(ApoE^(−/−))mice.Methods:Male ApoE^(−/−)mice were fed with a HFD or a normal diet(ND)for 15 weeks.On the first day of Week 13,the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells.At Weeks 12 and 15,serum lectin‐like oxidized low‐density lipoprotein receptor‐1(LOX‐1)and vascular endothelial growth factor levels were measured by enzyme‐linked immunosorbent assay,and blood monocytes and macrophages were measured by fluorescence‐activated cell sorting.At Week 15,the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured.Results:At Week 15,compared with mice in the ND group,those in the HFD group had a larger volume of local subcutaneous cancer(p=0.0004),heavier tumors(p=0.0235),more metastatic cancer in the lungs(p<0.0001),a larger area of lung involved in metastatic cancer(p=0.0031),and larger areas of atherosclerosis in the aorta(p<0.0001).At Week 12,serum LOX‐1,serum vascular endothelial growth factor,and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group(p=0.0002,p=0.0029,p=0.0480,and p=0.0106,respectively);this trend persisted until Week 15(p=0.0014,p=0.0012,p=0.0001,and p=0.0204).Conclusions:In this study,HFD‐induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse.HFD‐induced upregulation of LOX‐1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.

电针与单纯针刺治疗首发轻中度抑郁症临床疗效对比分析

目的比较电针和单纯针刺治疗首发轻中度抑郁症的临床疗效。方法将50例首发轻中度抑郁症患者随机分成电针组和针刺组各25例。两组针刺取穴相同,均为百会、四神聪、太阳(双侧)、印堂、合谷(双侧)。电针组于百会、印堂、太阳(双侧) 4穴接电针仪,频率为1 Hz,连续波。两组均每周治疗3次,持续6周,治疗后6个月进行随访。比较两组治疗前后汉密尔顿抑郁量表(HAMD)和抑郁自评量表(SDS)评分,随访时用HAMD进行评分。治疗后进行临床疗效评价。结果电针组最终纳入统计23例,针刺组最终纳入统计22例。电针组临床疗效总有效率为91. 3%,针刺组为68. 1%,两组总有效率比较差异无统计学意义(P=0. 16);两组治疗后HAMD总分及各因子评分均较本组治疗前降低(P <0. 05);两组睡眠障碍因子前后差值比较,差异有统计学意义(P=0. 01)。两组治疗后SDS评分均较本组治疗前降低(P <0. 05);两组SDS评分治疗前后差值比较,差异无统计学意义(P> 0. 05)。治疗后及随访时两组间HAMD评分比较,差异无统计学意义(P> 0. 05)。结论电针和单纯针刺治疗首发轻中度抑郁症疗效相当,且治疗后6个月疗效仍可以维持;在改善睡眠方面,电针更具有优势。