Bergapten attenuates D-galactose-induced immunosenescence in BALB/c mice

OBJECTIVE Bergapten(BG),is a furanocoumarin derived from herbal and citrus extracts can act as antioxidant and selective anticancer agents.The current study aimed to investigate whether bergapten would attenuate immunosenescence and to exploreits immunomodulatory effects on immune responses in D-galactose-induced aging BALB/c mice.METHODS Firstly,mice were given D-galactose(180 mg·kg^(-1)) subcutaneous injections for 30 d.To evaluate the establishment of the agingrelated effect in mice,serum samples of BALB/c mice were collected from tail vein.Aging BALB/c mice were freely divided into three groups:negative control group received 1% Tween 80 solution only,named D-gal group.Positive groups were received BG administration at the dose of 20 and 100 mg·kg^(-1),named D-gal+BG(20) group and D-gal+BG(100) group,respectively.Effects of bergapten on T lympho.cyte proliferation and flow cytometry were assessed by using the splenic cell suspension.Enzyme linked immunospot kits were used to quantitatively determine interferon-γ(IFN-γ) and interleukin-4(IL-4)levels of the isolated serum.Immunophenotype was determined by using mixture of antibodies includ.ing anti-CD3,anti-CD4,and anti-CD8.RESULTS Bergapten(20 mg·kg^(-1)) therapy can modulate immu.nity against viral epidemics and attenuate aging-induced immune deficiency(P<0.01),which was correlat.ed with the decline in the activation of the Th and Tc responses in D-galactose induced aging BALB/c mice.According to the in vivo results,bergapten exposure up-regulated the secretion of IFN-γ and IL-4 in T-helper 1(Th1) and T helper 2(Th2) cells(P<0.05,P<0.01).Additionally,BG(20 mg·kg^(-1)) restored antigen-specific CD4+ and CD8+ T cells in aging models(P<0.05,P<0.01),which may help to curing chronic infections.CONCLUSION The beneficial effect of bergapten in D-galactose induced aging BALB/c mice may be due to the Th and Tc responses activation.

Post-ischemic Elevation of Circulating Hepatocyte Growth Factor Differentiates Stroke from Transient Ischemic Attack

Background:A rapid elevation of post-ischemic circulating hepatocyte growth factor(HGF)levels has been reported in acute vascular disease including stroke.However,the impact of transient ischemic attack(TIA)on circulating HGF has never been studied.Methods:Patients with an onset of either stroke or TIA within the past 30 days were enrolled.Based on the ischemic event,the patients were divided into a stroke group and a TIA group.Blood samples were collected at enrollment and at follow-up visits at one,three,and six months until a recurrent cerebral ischemic event.Plasma levels of HGF were measured using an enzyme-linked immunosorbent assay and logarithmically transformed to eliminate skewness.Results:Thirty-six patients were enrolled in the study,with 20 in the stroke group and 16 in the TIA group.The dynamic HGF levels post-ischemia showed distinct patterns between the two groups.A significant decrease of HGF levels was observed in the stroke group,from 2.62±0.18 ng/mL within 30 days after stroke to 2.41±0.22 ng/mL beyond 30 days(P=0.026);however,no significant change was found in the TIA group(2.22±0.17 ng/mL vs.2.19±0.16 ng/mL,P=0.990).A multivariate regression analysis showed a last event of stroke and a comorbidity of systemic atherosclerotic disease(SAD)were independently associated with higher levels of HGF.Subgroup analyses showed HGF levels decreased from 2.64±0.22 ng/mL within 30 days after stroke to 2.36±0.18 ng/mL beyond 30 days in patients without SAD(P=0.008),but not in patients with SAD(P=0.700).Conclusion:Our data indicate that in patients without SAD,circulating HGF is a potential biomarker to distinguish between stroke and TIA.