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Objective:To explore the effects of different concentrations of 2-hydroxybenzylamine(2-HOBA)on atherosclerosis and vascular smooth muscle cell senescence and the underlying mechanisms.Methods:Fourteen apolipoprotein E-deficient(ApoE-/-)mice were used to establish an atherosclerosis model and were divided into two groups(n=7)using the random number method: a high-fat diet(HD)group and a high-fat diet plus 2-HOBA(1 mg/ml)(HD+ HOBA)group.Pulse wave velocity was used to assess vascular stiffness and a treadmill was used to assess exercise endurance.Oil Red O staining was used to detect the size and number of atherosclerotic plaques.Masson staining was used to detect the morphology of collagen fibers and elastic fibers in the plaque, the size of the necrotic core area of the plaque, and the thickness of the fibrous cap.Mouse smooth muscle cells were treated with different concentrations of 2-HOBA(100 μmol/L, 250 μmol/L and 500 μmol/L)to establish an H 2O 2-induced senescence model.Senescence-associated β-galactosidase staining was used to detect cell senescence.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression levels of senescence-related secretory phenotype factors, and Western blot was used to detect the expression levels of senescence-related signaling proteins. Results:Compared with the HD group, the HD+ HOBA group showed that the area and number of aortic atherosclerotic plaques were decreased, and the atherosclerotic plaques were stabilized.In addition, compared with the HD group, vascular stiffness in the HD+ 2-HOBA group decreased by 26%(2.59±0.32 mm/ms vs.3.50±0.28 mm/ms), with a statistically significant difference( P<0.01), and exercise endurance increased by 62%[(143.74±24.25)m vs.(233.50±30.21)m, P<0.01], suggesting that 2-HOBA was able to improve aortic vascular stiffness and exercise endurance in mice.2-HOBA ameliorated H 2O 2-induced vascular smooth muscle cell senescence and decreased the mRNA levels of H 2O 2-induced senescence-associated secretory phenotype factors such as interleukin-1β, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1.Meanwhile, 2-HOBA also inhibited the expression of p53 and p21, the key signaling factors of senescence. Conclusions:2-HOBA suppresses the development and progression of atherosclerosis through inhibiting oxidative stress-related p53/p21 signaling activation and ameliorating vascular smooth muscle cell senescence and the aging-related inflammatory phenotype.
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Edong Healthcare Group is cited as an example to introduce the founding background, and summarize its successful practices and outcomes in corporate governance, internal operation management mechanism, and optimized resources deployment within the group.Win-win mechanism is proposed as the key to a successful grouping reform, and further experiment with the hierarchical medical system is recommended for deeper reform in building groups of public hospitals.
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Objective To determine co-author contribution for a biomedical scientific paper describing collaborative research by an analytical process model.Methods The important features of contribution were identified,categorized and organized into a logical hierarchy consisting of the main dimensions and sub-dimensions.A face-to-face survey was conducted to obtain data about their relative importance from co-authors.Analytical hierarchy process methodology was used to determine the relative important weights from main dimensions and sub-dimensions along with the consistency.Results Among the 5 main dimensions,all authors considered problem statement as the most important with a weight of 0.4355,and considered research design and data analysis taking the 2nd and 3rd positions.Among the 10 sub-dimensions,hypothesis construction,method development,result interpretation,and critical revision of manuscript were considered the most important contributions.Conclusion Analytical hierarchy process effectively supportto establish the co-authors' priorties for a biomedical scientific paper.
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Objective To investigate the expression of TMS1/ASC gene induced by gemcitabine(GEM) in pancreatic carcinoma cell line PANC-1.To study the relationship between cysteine aspartase(caspase-1),nuclear factor-κB(NF-κB) and the expression of TMS1/ASC.Methods The pancreatic carcinoma cell line PANC-1 was cultured in Dnlbecco's modification of Eagle's medium(DMEM).Methyl thiazolyl tetrazolium (MTT)method was used to measure the effect of GEM at different time points(24,48 h)at different concentrations(1,2,4,8,16 μg/ml) on growth of PANC-l.RT-PCR was used to detect the expression of TMS1/ASC mRNA stimulated by medium alone and by GEM(4.27μg/ml)for 24 h and 48 h.Western blot analysis was performed with inhibitory protein of NF-κB multiclonal antibody,caspase-1 multiclonal antibody and β-actin monoclonal antibody to observe the expression of β-actin,caspase-1 and IκBα in GEM group and in the control group.The activation state of caspase-1 and NF-κB was examined.Results GEM inhibited the growth of PANC-1 cells in a concentrationand-time-dependent manners and its half maximal inhibitory concentration(IC50)was 4.27 μg/ml on 24 h.The expression of TMS1/ASC was 0.3 ±0.004 and 0.63 ±0.007 respectively in GEM group while it was 0.1 ±0.001 and 0.21 ± 0.006 in the control group on 24h and 48h.The difference between the 2 groups at the same time point had statistical significance (P ＜ 0.01).Western blot showed that GEM caused the activation of caspase-1.The expression of IκBα had no obvious differencebetween the 2 groups.GEM couldn't induce the activation of NF-κB.Conclusions GEM can inhibit proliferation of PANC-1 cells and induce their apoptosis.The drug sensitivity decreased with prolongation of exposure time.GEM might induce and increase the expression of TMS1/ASC,which might influence the apoptosis of the cells later.The apoptosis of PANC-1 cells induced by GEM is dependent of caspase-1 signaling pathway and independent of NF-κB signaling pathway.
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OBJECTIVE:To study the spermicidal and antibacterial effects of tannic acid from Chinese gall.METHODS:Human sperm samples of 20 subjects were taken for spermicidal tests in vitro in accordance with the standard method recommended by WTO.The minimum inhibitory concentration and minimum bactericidal concentration(MIC and MBC)of tannic acid from Chinese gall on bacterium coli and staphylococcus aureus were detected.RESULTS:The lowest effective spermicidal concentration of tannic acid at 20s was 20mg? mL-1.The MIC and MBC of tannic acid against bacterium coli(3 strains)were 0.195～ 0.390mg? mL-1 and 0.390～ 0.780 mg? mL-1 respectively,against staphylococcus aureus(2 strains)were 0.049～ 0.098mg? mL-1 and 0.195～ 0.390mg? mL-1 respectively.CONCLUSION:Tannic acid from Chinese gall showed potent coagulating effect on spermatines and remarkable antibacterial effect,and which is expected to be an effective and safe vaginal spermicidal and antibacterial agent,further study on which remains to be carried out.