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BACKGROUND:Sodium butyrate, a histone deacetylase inhibitor, can inhibit cell proliferation, and induce apoptosis and differentiation of various cancer cells. However, the role of sodium butyrate combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on lung cancer stem cells remains unclear. OBJECTIVE:To explore the effect of sodium butyrate combined with TRAIL on biological behaviors of lung cancer stem cells. METHODS:Magnetic bead separation was used to separate lung cancer stem cells (CD133+) from human lung adenocarcinoma A549 cells. After the lung cancer stem cells were treated with simple DMEM/F12, DMEM/F12 containing sodium butyrate (5 mmol/L), TRAIL (50 μg/L) or sodium butyrate combined with TRAIL, the cell proliferation within 96 hours of culture was determined by MTT assay; the apoptosis within 24 hours of culture was measured by flow cytometry; the cell migration within 48 hours of culture was detected by cell scratch test; the expression levels of pluripotent transcription factors (Oct4, Sox2 and Nanog) within 48 hours of culture were detected using western blot analysis. RESULTS AND CONCLUSION:The CD133+ lung cancer stem cells were successfully enriched from human lung adenocarcinoma A549 cells. MTT assay showed that sodium butyrate and TRAIL significantly inhibited the proliferation of lung cancer stem cells (P< 0.05), and the combination effect was even stronger (P < 0.05). Results from flow cytometry analysis and scratch test showed that sodium butyrate or TRAIL induced apoptosis and inhibited cell migration of lung cancer stem cells (P < 0.05), and the combination of sodium butyrate and TRAIL showed a stronger effect (P < 0.05). In addition, the expression levels of Oct4, Sox2 and Nanog were significantly down-regulated by sodium butyrate (P < 0.05), TRAIL or sodium butyrate combined with TRAIL, and the combination effect was stronger (P < 0.05). In conclusion, sodium butyrate and TRAIL have synergistic effects on lung cancer stem cells, indicating a new way for treatment of lung cancer.
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Objective To explore the changes of deceleration capacity of rate (DC) and analyze its correlation with heart rate variability (HRV) and other factors in patients with coronary heart disease. Methods One hundred and twenty-nine patients with coronary heart disease (coronary heart disease group) and 109 healthy people (control group) were enrolled in this study. DC and HRV parameters were measured by using digitized 24 h Holter. The correlation between DC and HRV parameters, other factors were analyzed. Results The levels of DC, SDNN, SDANN, SDNNi, PNN50, TP, LF, HF, AC in coronary heart disease group were significantly lower than those in control group:(5.64±1.67) ms vs. (6.71±1.47) ms, (106.60±20.53) ms vs. (138.82±31.22) ms, (96.94±20.06) ms vs. (127.47±31.87) ms,(28.53±14.75) ms vs. (52.24±14.65) ms, 87.72%vs. 103.86%,(1 967.10±966.16) ms2/Hz vs. (2 846.70±1 443.41) ms2/Hz,(326.43±195.35) ms2/Hz vs.(457.64±254.30) ms2/Hz, 85.88 vs. 106.39, (-6.18±2.15) ms vs. (-7.00±2.51) ms, P<0.05 or<0.01. DC was correlated with SDNNi, PNN50,TP,LF, HF, AC both in total population or in coronary heart disease group and control group by using multiple linear correlation analysis ( r=0.586, 0.356, 0.531, 0.563, 0.435,-0.433, P<0.01). After removing confounders, DC was correlated with age, SDNNi, rMSSD, PNN50 and AC (P<0.01). Conclusions DC decreases in patients with coronary heart disease and is strong correlativity with HRV parameters. DC could be used for quantitative detection of autonomic nervous function.
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Objective To explore the correlation between cystatin C (Cys C) and intima-media thickness of carotid artery (CIMT) in patients with hypertension.Methods One hundred and one patients with hypertension (hypertension group) and 54 healthy people (control group) were enrolled in this study.The level of serum Cys C was measured and CIMT was detected by B ultrasound.The correlation between Cys C and CIMT was analyzed.Results The level of Cys C and CIMT in hypertension group were significantly higher than those in control group [(0.92 ±0.21) mg/L vs.(0.85 ±0.20) mg/L,(0.91 ±0.16) mm vs.(0.65 ± 0.15) mm] (P ＜ 0.05 or ＜ 0.01).Multiple linear correlation analysis showed that Cys C and CIMT was positively correlated in total population or hypertension group or control group (r =0.412,0.443,0.315,P ＜0.01).Conclusion Serum Cys C is associated with the degree of hypertension arteriosclerosis,and Cys C may be involved in atherosclerosis.
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Objective To explore the expressive level and clinical significance of tumor necrosis factor ligands related molecule 1A (TL1A) in peripheral blood of patients with viral myocarditis.Methods In 70 patients with viral myocarditis (viral myocarditis group) and 70 normal controls (control group),the plasma level of TL1A was detected by enzyme linked immunosorbent assay and the mRNA level of TL1A was detected by real-time quantitative reverse transcription polymerase chain reaction.Results The plasma level of TL1A in viral myocarditis group was significantly higher than that in control group [(1.37 ± 0.41) μg/L vs.(0.85 ± 0.22) μg/L](P=0.000).The level of peripheral blood TL1A mRNA in viral myocarditis group was significantly higher than that in control group (0.39 ±0.17 vs.0.31 ±0.11,P =0.001).Conclusion The level of TL1A in patients with viral myocarditis is increased,and TL1A may participate in the occurrence of viral myocarditis.
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Objective To investigate the changes of peripheral blood Foxp3+ regulatory T cell (Treg cell) in patients with ovarian cancer (OC).Methods In 46 patients with OC and 46 normal controls,the percentage of peripheral blood CD4+ Foxp3+ Treg cell was assessed by flow cytometry and Foxp3 mRNA level was detected by real-time quantitative reverse transcription polymerase chain reaction.The level of plasma.transforming growth factor β1 (TGF-ββ 1) was measured by enzyme linked immunosorbent assay.Results The percentages of CD4+ Foxp3+ Treg cell,Foxp3 mRNA and level of plasma TGF-β1 in patients with OC were statistically higher than those in normal controls [(11.42 ± 2.67)％ vs.(8.94 ± 1.98)％,0.59 ± 0.21 vs.0.37 ±0.14,(35 580 ±7274) ng/L vs.(28 610 ±5631) ng/L,P=0.0000].Conclusion The number and/or function of CD4+ Foxp3+ Treg cell in peripheral blood of patients with OC are abnormal,CD4+ Foxp3+Treg cell may participate in the occurrence of OC.
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Objective To evaluate the effect of alendronate on osteoprotegerin (OPG) and receptor of activator of nuclear factor κB-ligand (RANKL) expression in human marrow stroma cells (hMSCs) in vitro. Methods hMSCs were isolated from haman marrow, cultured in vitro, and randomly divided into two groups: alendronate group, hMSCs culture fluid containing 1×10-7 mol/ L alendronate; control group, no special treatment but culturing hMSCs in DMEM. Two weeks after treatment, the expressions of OPG and RANKL were evaluated by RT-PCR and Western blot.Results hMSCs became uniform spindle-shaped fibroblasts. As cells proliferated, they formed colonies and showed whirlpool arrangement. After one week's treatment, hMSCs in alendronate group had reduced processes and gradually showed disc shape, which did not happen in control group but kept fibroblast shape and just increased in density. In RT-PCR, the ratio of OPG/RANKL in alendronate group and control group was 8.77±1.16 and 4.58±1.27, respec-tively. In Western blot, the ratio of OPG/RANKL in alendronate group and control group was 2.58±0.47 and 1.52±0.32, respectively. The ratio of OPG/RANKL was higher in alendronate group than in control group (P<0.01).Conclusion Alendronatc enhances OPG expression and inhibits RANKL expression of hMSCs in vitro.