1.Detection of plasma RANTES, eotaxin, TNF-α and LTB4 in patients with chronic urticaria
Lihong SHI ; Xiaomin LI ; Jinyong LI ; Huaguang MU
Chinese Journal of Dermatology 2009;42(8):553-555
Objective To investigate the plasma levels of regulated upon activation normal T cell expressed and secreted (RANTES), eotaxin, tumor necrosis factor (TNF)-α and leukotriene B4 (LTB4) in patients with chronic urticaria and their roles in the pathogenesis of chronic urticaria. Methods Forty-one patients with chronic urticaria were included into this study along with 20 normal human controls. Patients were graded into three groups, I.e. Mild group (n = 11), moderate group (n = 21) and severe group (n = 9), according to their symptom score. All patients were treated with mizolastine 10 mg per day for 4 weeks. ELISA was used to study the plasma levels of RANTES, eotaxin, TNF-α and LTB4 in normal controls and patients before and after treatment. Results The plasma levels of RANTES, eotaxin, TNF-α and LTB4 were (52.5 ± 10.2) g/L, (58.4 ± 16.1) g/L, (35.1 ± 9.6) ng/L and (109.4 ± 21.7) ng/L, respectively, in untreatedpatients with chronic urticaria, compared to (33.7 ± 9.4) g/L, (48.3 ± 13.6) g/L, (21.3 ± 8.9) ng/L and(77.8 ± 11.6) ng/L, respectively, in normal controls(P < 0.01, 0.05, 0.01, 0.01, respectively). Increased plasmalevels of RANTES, eotaxin, TNF-α and LTB4 were observed in patients with moderate or severe chronic urticaria compared with those with mild chronic urticaria (both P < 0.05), whereas there was no significant difference between patients with severe and mild chronic urticaria (P < 0.05). After treatment with mizolas-fine the plasma levels ofRANTES, eotaxin, TNF-α and LTB4 were (36.3 ± 8.9) g/L, (46.3 ± 10.2) g/L, (23.2 ± 7.5) ng/L and (83.1 ± 14.2) ng/L respectively, significantly lower than those in patients before treatment (all P < 0.01), but showed no difference from those in normal controls (all P > 0.05). Conclu-sions The plasma levels of RANTES, eotaxin, TNF-α and LTB4 are elevated in patients with chronic urticaria, and they exhibits a positive correlation tendency with disease activity. After treatment with mizolastine, a significant decrease is observed in the plasma levels of RANTES, eotaxin, TNF-α and LTB4, which hints that RANTES, eotaxin, TNF-α and LTB4 may play a certain role in the pathogenesis of chronic urticaria.
2.Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway.
Dan MU ; Huaguang QIN ; Mengjie JIAO ; Shaogui HUA ; Tingzhe SUN
Journal of Zhejiang University. Science. B 2021;22(2):123-135
Ischemic stroke presents a leading cause of mortality and morbidity worldwide. Theaflavic acid (TFA) is a theaflavin isolated from black tea that exerts a potentially neuro-protective effect. However, the dynamic properties of TFA-mediated protection remain largely unknown. In the current study, we evaluated the function of TFA in the mitochondria apoptotic pathway using mathematical modeling. We found that TFA-enhanced B-cell lymphoma 2 (Bcl-2) overexpression can theoretically give rise to bistability. The bistability is highly robust against parametric stochasticity while also conferring considerable variability in survival threshold. Stochastic simulations faithfully match the TFA dose response pattern seen in experimental studies. In addition, we identified a dose- and time-dependent synergy between TFA and nimodipine, a clinically used neuro-protective drug. This synergistic effect was enhanced by bistability independent of temporal factors. Precise application of pulsed doses of TFA can also promote survival compared with sustained TFA treatment. These data collectively demonstrate that TFA treatment can give rise to bistability and that synergy between TFA and nimodipine may offer a promising strategy for developing therapeutic neuro-protection against ischemic stroke.