Anti-asthmatic effect of Ping-Chuan Formula in asthmatic mice, and its molecular mechanism of action

Purpose: To investigate the anti-asthmatic effect of Ping-Chuan Formula (PCF) in a mouse model, and the associated molecular mechanisms.Methods: Asthma mice were induced using ovalbumin (OVA), and PCF (600 mg/kg) was administered to the mice for 4 weeks. Sections of lung tissues were examined microscopically. The expressions of interleukins (ILs), interferon (IFN)-γ, transforming growth factor (TGF)-β were assayed, while lung tissue expressions of Toll like receptor (TLR)-4, GATA binding protein (GATA)-3, Ox40 ligand (OX40L), indoleamine 2,3-dioxygenase (IDO), and forkhead box P3 (Foxp3) determined. The T box expressed in T cells (T-bet) was evaluated using western blotting. The expressions of MHC II and co-stimulators (CD 11c, CD 80 and CD 86) of dendritic cells (DCs) were determined by flow cytometry.Results: PCF decreased inflammation in lung, and also down-regulated IL-4, -6, -17 and TGF-β (p < 0.01), whereas IL-10 and IFN-γ expressions were up-regulated (p < 0.01). Moreover, PCF decreased the expressions of TLR-4, GATA-3 and OX40L in lung tissue, and promoted Foxp3, IDO and T-bet. Besides, PCF decreased the levels of MHC II and co-stimulators (CD 80 and CD 86) on the surface of DCs.Conclusion: PCF exerts anti-asthmatic effect in mice via inhibition of inflammation, and modulation of MHC II and co-stimulators on the surface of DCs. These findings suggest that PCF is a promising candidate drug for treating asthma in humans

Effects of tMa-Xin-Di-Tan decoction on ovalbumin-induced allergic asthma in mice

Purpose: To investigate the effect of the Ma-Xin-Di-Tan (MXDT) decoction on  ovalbumin-induced allergic asthma (AA) in mice.Methods: Asthma was induced in mice by ovalbumin (OVA) injection, and different doses of MXDT (150, 300, and 600 mg/kg/day) were administered orally for 28 days. Pathological changes in lung tissues were examined, while levels of cytokines, including interleukin (IL)-4, IL-6, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-β, were determined using enzyme-linked immunosorbent assays (ELISAs) of the bronchoalveolar lavage fluid. Toll-like receptor (TLR)-4,  GATA-binding protein (GATA)-3, Ox40 ligand (OX40L), indoleamine  2,3-dioxygenase (IDO), forkhead box P3 (Foxp3), and T box expressed in T cells (T-bet) levels were determined in lung tissues by western blot analysis.Results: MXDT inhibited the inflammatory reaction of lung tissues in  OVA-challenged mice. After treatment with MXDT, levels of IL-4, IL-6, IL-17, and TGF-β were downregulated, whereas IFN-γ levels were upregulated. In addition,  MXDT decreased TLR-4, GATA-3, and OX40L levels in lung tissues but increased the expression of Foxp3, T-bet, and IDO.Conclusion: MXDT has antiallergic effects on OVA-induced AA in mice; the possible molecular mechanisms might involve the inhibition of inflammatory reactions and modulation of Th1/Th2 cytokine balance.Keywords: Ma-Xin-Di-Tan decoction, Allergic asthma, Inflammatory reactions, Th1/Th

N-(4-hydroxyphenyl) retinamide inhibits migration of renal carcinoma cells and promotes autophagy via MAPK p38 pathway

Purpose: To investigate the effect of N-(4-hydroxyphenyl) retinamide (4HPR) on autophagy and migration of renal carcinoma cells.Methods: Renal cancer cell lines were treated with various concentrations of 4HPR. Proliferation of the cells was studied using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltrazolium bromide (MTT), while apoptosis and cell cycle arrest were determined by flow cytometry.Results: Treatment of RCCs with 30 μM 4HPR caused significant inhibition of viability. In 786-O and OS-RC-2 cell lines, 4HPR reduced colony formation by 39 and 43 %, respectively. In addition, 4HPR increased the percentage of 786-O cells in G1 phase from 58.79 ± 3.43 to 71.68 ± 4.47 % (p < 0.05). It also decreased the percentage of cells in the S-phase from 21.98 ± 2.78 to 09.17 ± 1.43 %, and enhanced the activation of p38 and JNK in 786-O cells at 48 h. Western blot assay showed that the activation of p38 and JNK by 4HPR was inhibited on pre-treatment with SB203580 (inhibitor of p38) and SP600125 (inhibitor of JNK), respectively. Reduction of 786-O cell viability by 4HPR treatment was also significantly inhibited by pre-treatment with sp203580 and sp600125 (p < 0.05). Furthermore, the inhibitors also reversed the effect of 4HPR on the expressions of Bax and Bcl-2 in 786-O cells.Conclusion: These results indicate that 4HPR inhibits the growth of renal cancer cells via activation of MAPK signalling pathway. Thus, 4HPR is a potential drug target for management of renal cancer.Keywords: Retinamide, Renal cancer, Autophagy, MAPK signalling, Cell proliferation, N-terminal kinas

Effect of Pingchuan Formula on Toll-Like Receptors and Dendritic Cells in an Asthmatic Mouse Model

Pingchuan formula (PCF) was created by Professor Yu Jianer. The purpose of this study was to investigate the effect of PCF on dendritic cells (DCs) and toll-like receptors (TLRs) in initiating immunity. A bronchial asthma BALB/c mouse model was established using an OVA excitation method. PCF was immediately administered by gavage after the first excitation. After 7 d, hematoxylin and eosin (HE) staining was used to observe the pathological changes in the asthma model. Eosinophil infiltration and concentrations of IL-4, IFN-r, IL-12, and IFN-α in BALF were determined by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to determine mRNA levels of IL-12 and IFN-α. Protein expression levels of ERK, Toll-2, IDO, and Toll-9 were measured by immunoblot. HE and ELISA showed that PCF could improve lung pathological changes and significantly decrease the concentration of IL-4 in BALF. Moreover, PCF could increase IL-12, IFN-α, and IFN-r in BALF. Real-time PCR and western blot showed that PCF restored the DCs and TLRs in initiating immunity. In summary, this study found that PCF can improve the pathological changes and reduce the symptoms of asthma in a BALB/c mouse model. It can facilitate the initiation of immunity by restoring the DCs and TLRs

Inflammatory Immune Process and Depression-like Behavior in Hypothyroid Rats: A [¹⁸F] DPA-714 Micro Positron Emission Tomography Study

Hypothyroidism is closely related to mental disorders, mainly depression, through an as-yet-unknown mechanism. The cerebral inflammatory immune process has been implied to play a pivotal role in the onset of affective symptoms in several conditions. In order to gain insight into the mechanism underlying the depressive behaviors in hypothyroid rats, brain microglial activation was evaluated using micro positron emission tomography imaging with a translocator protein (TSPO) radioligand. Hypothyroidism was induced in adult male Wistar rats by administration of 0.05% propylthiouracil in drinking water for five weeks. Open field, forced swimming and tail suspension tests were employed to evaluate the depressive behavior in hypothyroid rats, and the relationship between the behavioral changes and brain microglial activation was evaluated using [18F] DPA-714 micro positron emission tomography imaging. The open field test revealed significantly reduced first-minute activity and rearing behavior in the hypothyroid group, as well as significantly increased immobility in the forced swimming test and the tail suspension test. Hypothyroidism induced significantly increased microglial activation in the hippocampus. The radioligand uptake in the hippocampus correlated negatively with first-minute activity in the open field test (p p < 0.05). Immunohistochemistry also confirmed the activation of microglia and inflammatory bodies in hypothyroid rats. The results indicate that hypothyroidism can induce depressive behavior in adult Wistar rats, microglial activation in the hippocampus plays an important role in the depressive behavior in hypothyroid rats and the inflammatory immune mechanism may underlie the behavioral abnormalities in thyroid dysfunction. Furthermore, the findings in the present study suggest there might be a common mechanism underlying depressive behavior in adult-onset hypothyroidism and depression

A DIVIDE-AND-CONQUER METHOD FOR 3D CAPACITANCE EXTRACTION Approved as to style and content by:

This thesis describes a divide-and-conquer algorithm to improve the 3D boundary element method (BEM) for capacitance extraction. We divide large interconnect structures into small sections, set new boundary conditions using the border for each section, solve each section, and then combine the results to derive the capacitance. The target application is critical nets where 3D accuracy is required. The new algorithm is a significant improvement over the traditional BEMs and their enhancements, such as the “window ” method where conductors far away are dropped, and the “shield ” method where conductors hidden behind other conductors are dropped. Experimental results show that our algorithm is 25 times faster than the traditional BEM and 5 times faster than the window+shield method, for medium to large structures. The error of the capacitance computed by the new algorithm is within 2 % for self capacitance and 7 % for coupling capacitance, compared with the results obtained by solving the entire system using BEM. Furthermore, our algorithms gives accurate distributed RC, where none of the previous 3D BEM algorithms and their enhancements can