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Objective:To investigate the effects and potential mechanisms of resveratrol on obesity in elderly mice.Methods:In this study, 3 groups were randomly formed for 32-week-old mice and for 48-week-old mice.The normal diet group received regular chow and 0.3 ml saline by gavage once a day, the high-fat diet group received a high-fat diet(containing 21% fat and 1.25% cholesterol)and 0.3 ml saline once a day, and the high-fat diet plus resveratrol group received a high-fat diet and resveratrol(22.4 mg/kg, dispersed in 0.3 ml saline)by gavage once a day.After 12 weeks, body weight and adipose tissues were measured.Plasma leptin concentrations were determined by an enzyme-linked immunosorbent assay(ELISA), and values for hypertrophic obesity-related indexes of mice were obtained by quantitative real-time PCR.Results:The body weight and the proportion of subcutaneous fat tissues were lower in the high-fat diet plus resveratrol group than in the high-fat diet group[(34.43±3.23)g vs.(53.16±2.16)g, (3.21±1.58)% vs.(4.86±0.64)%, P<0.01], and were similar to those in the normal diet group.Resveratrol had a more obvious inhibitory effect on leptin in elderly mice than in middle-aged mice.In elderly mice, the plasma leptin concentration was lower in the high-fat diet plus resveratrol group than in the high-fat diet group[(0.015±0.009)g/L vs.(0.100±0.027)g/L]and the normal diet group( F=19.85, P=0.001), and it was similar to that in the middle-aged mice on a normal diet.Resveratrol significantly increased the expression of peroxisome proliferator-activated receptor gamma(PPARγ)and glucose transporter 4(GLUT4)and reduced the expression of tumor necrosis factor-α(TNF-α)( F=10.79, 9.31 and 7.02, P=0.003, 0.006 and 0.010). Conclusions:Resveratrol can significantly improve hypertrophic obesity in elderly mice, and the inhibition of leptin secretion and up-regulation of PPARγ may be the key mechanisms.
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Objective:To investigate the effects of lithium chloride on vascular smooth muscle cell calcification and the potential underlying mechanisms.Methods:Human aortic smooth muscle cells were cultured in vitro, and a smooth muscle cell calcification model was established by using a calcification medium(the concentration of inorganic phosphorus was 3 mmol/L). Cells in the drug treatment group were pretreated with lithium chloride(10 mmol/L)for 4 hours and then with inorganic phosphorus at 3 mmol/L.After several days in culture, calcium deposition in cells was measured by alizarin red S staining.The secretion of extracellular pyrophosphate was detected by measuring nicotinamide adenine dinucleotide hydrogen(NADH) consumption of pyrophosphate-coupled enzyme reactions, which were monitored spectrophotometrically at 340 nm.Real-time PCR and Western blotting were used to detect mRNA and protein expression of the human progressive ankylosis( ankh)gene.Human aortic smooth muscle cells were infected with the scramble control lentivirus and the sh- ankh lentivirus, respectively, to establish the control cell group and the ankh knockdown cell group.The effects of ankh knockdown on cell calcification were examined. Results:The calcification level in vascular smooth muscle cells increased in the high inorganic phosphorus group, compared with the control group[(65.00±2.11)ng/g vs.(12.39±0.38)ng/g, P<0.01)]. Compared with the high-phosphorus control group, lithium chloride evidently inhibited high phosphate-induced vascular smooth muscle cell calcification[(24.92±1.87)ng/g vs.(60.94±4.51)ng/g, P<0.01)]. Lithium chloride pretreatment clearly increased extracellular pyrophosphate levels under unstimulated conditions[(51.70±7.26)×10 -3mmol/g vs.(28.71±2.55)×10 -3mmol/g( P<0.01)]and under high phosphorus stimulation[(34.35±4.27)×10 -3mmol/g vs.(20.89±4.93)×10 -3mmol/g( P<0.05)], and increased the expression of ankh as well( P<0.01). In addition, ankh knockdown markedly enhanced the extent of inorganic phosphorus-induced vascular smooth muscle cell calcification(71.73±2.45 ng/g vs.56.19±3.59 ng/g, P<0.01). Conclusions:Lithium chloride inhibits high phosphorus-induced vascular smooth muscle cell calcification by enhancing the level of extracellular pyrophosphate via increased ankh expression.
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Survivin, a new member of inhibitors of apoptosis proteins(IAP) family, regulates the essential cellular processes, including inhibition of cell apoptosis, promotion of cell proliferation and tumor stromal angiogenesis. Survivin is undetectable in most terminally differentiated tissues, but upregulated in almost all types of human malignancies and its aberrant overexpression positively correlates with chemotherapy resistance, increased tumor recurrence and shortened patient survival. Because of its key role in tumor formation and development, Survivin is considered as an ideal target for anticancer treatment. This review discussed the molecular function of Survivin, relationship between Survivin and cancer biological characteristics, as well as the research progress of cancer therapy targeting Survivin.