Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome

AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's corre-lation analysis. SERT function was examined by tritiated serotonin(5-HT) uptake experiments. Rat intestinal epithelial cells(IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor(EGFR).RESULTS: EGF levels were significantly lower in th rats with visceral hypersensitivity as measured in plas ma(2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, < 0.01) and in colonic tissue(3.244 ± 0.135 ng/10 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P 0.01) compared with controls. Moreover, the EGF leve were positively correlated with SERT levels(r = 0.820 P < 0.01). EGF displayed dose- and time-dependen increased SERT gene expressions in IEC-6 cells. A EGFR kinase inhibitor inhibited the effect of EGF o SERT gene upregulation. SERT activity was enhance following treatment with EGF(592.908 ± 31.515 fmo min per milligram vs 316.789 ± 85.652 fmol/min pe milligram protein, P < 0.05) and blocked by the EGF kinase inhibitor in IEC-6 cells(590.274 ± 25.954 fmo min per milligram vs 367.834 ± 120.307 fmol/min pe milligram protein, P < 0.05).CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.

Compound Kushen injection induces immediate hypersensitivity reaction through promoting the production of platelet-activating factor via de novo pathway

OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.

A probabilistic power flow calculation method considering the uncertainty of the static frequency characteristic

In a power system, power generation and load have frequency response characteristics, which randomly fluctuate with changes in operating status. This study investigates a probabilistic power flow method that considers the unit and load uncertainty of the static frequency characteristic. Firstly, a calculation model is established on the basis of the characteristics of the frequency modulation performance of the unit and load. Then a calculation method is developed using the concept of dynamic power flow in order to determine the probability distribution of the active power flow of each line under the occurrence of a fault in the system. In the method, Monte Carlo sampling with the semi-invariant method is applied for analysis and calculation. The IEEE-30-buses system is taken as an example to analyze the impact of different responses of units on the power flow distribution of various branches. The method discussed herein is compared with the Monte Carlo simulation method to verify its effectiveness.

Unsupervised robust adaptive filtering against impulsive noise

An implementation of adaptive filtering, composed of an unsupervised adaptive filter （UAF）, a multi-step forward linear predictor （FLP）, and an unsupervised multi-step adaptive predictor （UMAP）, is built for suppressing impulsive noise in unknown circumstances. This filtering scheme, called unsupervised robust adaptive filter （URAF）, possesses a switching structure, which ensures the robustness against impulsive noise. The FLP is used to detect the possible impulsive noise added to the signal, if the signal is ＂impulse-free＂, the filter UAF can estimate the clean sig- nal. If there exists impulsive noise, the impulse corrupted samples are replaced by predicted ones from the FLP, and then the UMAP estimates the clean signal. Both the simulation and experimental results show that the URAF has a better rate of convergence than the most recent universal filter, and is effective to restrict large disturbance like impulsive noise when the universal filter fails.

High Temperature Deformation Behavior of 4340 Steel: Activation Energy Calculation and Modeling of Flow Response

The 4340 steel is extensively utilized in several industries including automotive and aerospace for manufac- turing a large number of structural components. Due to the importance of thermo-mechanical processing in the pro- duction of steels, the dynamic recrystallization （DRX） characteristics of 4340 steel were investigated. Namely, hot compression tests on 4340 steel have been performed in a temperature range of 900-- 1200 ℃ and a strain rate range of 0.01--1 s-1 and the strain of up to 0.9. The resulting flow stress curves show the occurrence of dynamic recrys- tallization. The flow stress values decrease with the increase of deformation temperature and the decrease of strain rate. The microstrueture of 4340 steel after deformation has been studied and it is suggested that the evolution of DRX grain structures can be accompanied by considerable migration of grain boundaries. The constitutive equations were developed to model the hot deformation behavior. Finally based on the classical stress-dislocation relations and the kinematics of the dynamic recrystallization; the flow stress constitutive equations for the dynamic recovery period and dynamic reerystallization period were derived for 4340 steel, respectively. The validity of the model was demon- strated by demonstrating the experimental data with the numerical results with reasonable agreement.