Cyclophilin A Plays Potential Roles in a Rat Model of Asthma and Suppression of Immune Response.

PURPOSE: Cyclophilin A (CypA) inhibits CD4+ T cell signal transduction via interleukin-2-inducible T-cell kinase (Itk), a tyrosine kinase required for T helper (Th) 2 cells function. Furthermore, mice with CypA silencing developed allergic diseases associated with increased Th2 cytokines production. CD4+ T cells with a Th2-cytokine pattern have been demonstrated to have a pivotal role in the pathogenesis of asthma. However, the effects of CypA in regulating immunity in asthma and in relieving asthmatic symptoms in vivo are entirely unknown. METHODS: Recombinant CypA protein (rCypA) was generated and purified. Ovalbumin (OVA)-challenged asthmatic rats model and acetylcholine chloride (ACh)-induced contraction of tracheal spirals were established. The pulmonary resistance (RL) value of asthmatic rats in vivo and the isometric tension of tracheal spirals ex vivo were recorded by MFLab 3.01 software. The levels of Th1 and Th2 cytokines and the quantities of immunoglobulin (IgA, IgG, IgM and IgE) in the supernatants of rat spleen lymphocytes were detected and analysed by bio-plex Suspension Array System and ELISA, respectively. CD4+ T cells were separated by MicroBeads, and the levels of interleukin (IL)-4 and interferon-γ (IFN-γ) were detected by ELISA. RESULTS: rCypA (10 ng/kg) significantly reduced RL within 2-7 min in OVA-challenged asthmatic rats in vivo, and there were no significant differences compared with terbutaline (TB) and hydrocortisone (HC). Furthermore, rCypA (10 ng/mL) significantly reduced the isometric tension in the ACh-induced contraction of the tracheal spiral ex vivo, and the effect of rCypA was better than that of TB. Additionally, rCypA suppressed the secretion of both Th1 and Th2 cytokines, and the suppressive effects of rCypA were stronger than those of HC, especially on Th2 cytokines. CONCLUSION: These findings indicate that CypA may serve as a potential novel therapeutic strategy for asthma.

[Analysis of Compatibility Laws for Acupoint Selection of Acupuncture in Treating Diabetic Gastroparasis].

OBJECTIVE: To summarize and analyze the compatibility laws for acupoint selection of acupuncture in treating diabetic gastroparasis (DGP) in modern literatures of clinical researches. METHODS: Retrieved were literatures related to treating DGP by acupuncture or acupuncture combined other therapies from PubMed, CNKI, and WF from 1982 to 2014. Analyzed were frequency of acupoint use, meridians selected acupoints belonged to, regions selected, association laws of selected compatible acupoints. RESULTS: Retrieved were 35 with compatibility frequencies more than 15 listed as follows: compatibility frequency of Zusanli (ST36) and Zhongwan (CV12) was 33 (94.29%); compatibility frequency of Zusanli (ST36) and Neiguan (PC6) was 23 (65.71%), compatibility frequency of Zhongwan (CV12) and Neiguan (PC6) was 22 (62.86%), compatibility frequency of Zusanli (ST36), Zhongwan (CV12), and Neiguan (PC6) was 22 (62.86%); compatibility frequency of Zusanli (ST36) and Sanyinjiao (SP6) was 16 (45.71%); compatibility frequency of Zhongwan (CV12) and Sanyinjiao (SP6) was 16 (45.71%); compatibility frequency of Zusanli (ST36), Zhongwan (CV12), and Sanyinjiao (SP6) was 15 (42.86%). Meridians selected acupoints belonged to were sequenced as Foot Yangming Stomach channel, Ren channel, Foot Taiyang Bladder channel, and so on. Acupoints selected were mainly in lower limbs, chest and abdomen, waist and back. The compatibility of Zusanli (ST36) and Zhongwan (CV12) was the most often used with the highest frequency. CONCLUSIONS: The compatibility laws for acupoint selection of acupuncture in treating DGP were mainly dominated as upper-lower selection, three regions selection, local selection, anterior-posterior selection. The compatibility laws for acupoint selection of acupuncture along meridians were mainly dominated as the convergence points and exterior-interior meridian points.

Proteomic analysis reveals the deregulation of inflammation-related proteins in acupuncture-treated rats with asthma onset.

Although the beneficial effects of acupuncture in asthma treatment have been well documented, little is known regarding the biological basis of this treatment. Changes in the lung proteome of acupuncture-treated rats with asthma onset were comparatively analyzed using a two-dimensional gel electrophoresis (2DE) and mass-spectrometry- (MS-) based proteomic approach. Acupuncture on specific acupuncture points appeared to improve respiratory function and reduce the total number of leukocytes and eosinophils in bronchoalveolar lavage fluid in OVA-induced asthma onset. Image analysis of 2DE gels revealed 32 differentially expressed acupuncture-specific protein spots in asthma onset; 30 of which were successfully identified as 28 unique proteins using LC-MS/MS. Bioinformatic analyses indicated that these altered proteins are most likely involved in inflammation-related biological functions, and the functional associations of these proteins result in an inflammation signaling pathway. Acupuncture regulates the pathway at different levels by regulating several key nodal proteins, including downregulating of proinflammatory proteins (e.g., S100A8, RAGE, and S100A11) and upregulating of anti-inflammatory proteins (e.g., CC10, ANXA5, and sRAGE). These deregulated inflammation-related proteins may mediate, at least in part, the antiasthmatic effect of acupuncture. Further functional investigation of these acupuncture-specific effector proteins could identify new drug candidates for the prophylaxis and treatment of asthma.

Alteration of the proteome profile of the pancreas in diabetic rats induced by streptozotocin.

Type 1 diabetes mellitus (T1DM) is receiving increased attention. To obtain a better understanding of the mechanism underlying T1DM, we performed a proteomic study on a rat model induced by streptozotocin. Pancreatic proteins were separated by two-dimensional gel electrophoresis. Eighteen protein spots were differentially expressed (P<0.05) with 2-fold or more increased or decreased intensity in the diabetic rats as compared with controls, of which 11 protein spots were up-regulated and 7 protein spots were down-regulated. These protein spots were successfully identified by liquid chromatography-electrospray ionization tandem mass spectrometry. The 60 kDa heat shock protein, the carbonyl reductase 1 (Cbr1), the hydroxyacyl-CoA dehydrogenase, Δ(3,5),Δ(2,4)-dienoyl-CoA isomerase, the elongation factor 1-δ, the 26S protease regulatory subunit 7 and the transitional endoplasmic reticulum ATPase were up-regulated, while the 78 kDa glucose-regulated protein, peroxiredoxin 4 and plakoglobin were down-regulated. The expression change of Cbr1 which is closely related to diabetic complications was further validated by western blotting. Our results and those of the bioinformatics analysis suggest that oxidative stress, the Wnt pathway, fatty acid degradation and glucose transport may be closely related to T1DM.