Lung transcriptomics reveals the underlying mechanism by which aerobic training enhances pulmonary function in chronic obstructive pulmonary disease.

BACKGROUND: Aerobic training is the primary method of rehabilitation for improving respiratory function in patients with chronic obstructive pulmonary disease (COPD) in remission. However, the mechanism underlying this improvement is not yet fully understood. The use of transcriptomics in rehabilitation medicine offers a promising strategy for uncovering the ways in which exercise training improves respiratory dysfunction in COPD patients. In this study, lung tissue was analyzed using transcriptomics to investigate the relationship between exercise and lung changes. METHODS: Mice were exposed to cigarette smoke for 24 weeks, followed by nine weeks of moderate-intensity treadmill exercise, with a control group for comparison. Pulmonary function and structure were assessed at the end of the intervention and RNA sequencing was performed on the lung tissue. RESULTS: Exercise training was found to improve airway resistance and lung ventilation indices in individuals exposed to cigarette smoke. However, the effect of this treatment on damaged alveoli was weak. The pair-to-pair comparison revealed numerous differentially expressed genes, that were closely linked to inflammation and metabolism. CONCLUSIONS: Further research is necessary to confirm the cause-and-effect relationship between the identified biomarkers and the improvement in pulmonary function, as this was not examined in the present study.

Discovery of zolinium TSG1180 as a novel agonist of transgelin-2 for treating asthma.

Asthma is a complex and heterogeneous respiratory disease that causes serious social and economic burdens. Current drugs such as ß2-agonists cannot fully control asthma. Our previous study found that Transgelin-2 is a potential target for treating asthmatic pulmonary resistance. Herein, we discovered a zolinium compound, TSG1180, that showed a strong interaction with Transgelin-2. The equilibrium dissociation constants (KD) of TSG1180 to Transgelin-2 were determined to be 5.363 × 10-6 and 9.81 × 10-6 M by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Cellular thermal shift assay (CETSA) results showed that the thermal stability of Transgelin-2 increased after coincubation of TSG1180 with lysates of airway smooth muscle cells (ASMCs). Molecular docking showed that Arg39 may be the key residue for the binding. Then, the SPR result showed that the binding affinity of TSG1180 to Transgelin-2 mutant (R39E) was decreased by 1.69-fold. Real time cell analysis (RTCA) showed that TSG1180 treatment could relax ASMCs by 19 % (P < 0.05). Once Transgelin-2 was inhibited, TSG1180 cannot induce a relaxation effect, suggesting that the relaxation effect was specifically mediated by Transgelin-2. In vivo study showed TSG1180 effectively reduced pulmonary resistance by 64 % in methacholine-induced mice model (P < 0.05). Furthermore, the phosphorylation of Ezrin at T567 was increased by 8.06-fold, the phosphorylation of ROCK at Y722 was reduced by 38 % and the phosphorylation of RhoA at S188 was increased by 52 % after TSG1180 treatment. These results suggested that TSG1180 could be a Transgelin-2 agonist for further optimization and development as an anti-asthma drug.

Analysis of Acupoint Selection and Combinations in Acupuncture Treatment of Asthma Based on Data Mining.

OBJECTIVE: Asthma is a highly prevalent respiratory disease that remains difficult to control. Acupuncture, as an important alternative therapeutic modality in preventing and treating asthma, is widely used in the world due to its promising efficacy and safety. Although acupoint selection and combinations are critical to therapeutic effects of acupuncture, its fundamental rules for asthma have not been fully understood. Thus, using data mining, the present study aimed to discover the most effective acupoints and combinations in the acupuncture treatment of asthma. METHODS: Controlled clinical trials (CCTs) of acupuncture treatment for asthma were searched and retrieved from databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, and PubMed. Data regarding the main acupoints prescribed in these clinical trials was collected and quantified. A network analysis was performed to uncover the interconnections between the acupoints. Additionally, hierarchical clustering analysis and association rule mining were conducted to discover the potential acupoint combinations. RESULTS: A total of 183 CCTs were retrieved. Feishu (BL13), Dingchuan (EX-B1), Dazhui (GV14), Shengshu (BL23), Pishu (BL20), and Fengmen (BL12) appeared to be the most frequently used acupoints for asthma. While the Bladder Meridian of Foot Taiyang, the Governor Vessel, and the Conception Vessel, compared to other meridians, were found to be the more commonly selected meridians. In the acupoint interconnection network, Feishu (BL13), Fengmen (BL12), Dingchuan (EX-B1), and Dazhui (GV14) were defined as key node acupoints. Moreover, acupoint clustering analysis revealed the treatment principle of "facilitating the flow of the lung Qi, tonifying spleen and kidney, and treating both the symptoms and root causes." Association rule mining analysis demonstrated that the combination of Pishu, Shenshu, Feishu, and Dingchuan, as well as that of Feishu, Dazhui, and Fengmen were potential acupoint combinations that should be selected with priority in asthma treatment. CONCLUSION: Based on a data mining analysis of published CCTs, this study provides valuable information regarding the selection of the most effective acupoints and combinations for clinical acupuncture practice and experimental study aimed at the prevention and treatment of asthma.

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.

What Is the Appropriate Acupuncture Treatment Schedule for Chronic Pain? Review and Analysis of Randomized Controlled Trials.

BACKGROUND: Acupuncture is widely used for the treatment of chronic pain. Different protocols of acupuncture practice exist and lack agreement on the optimal schedule of acupuncture treatment. OBJECTIVE: To review the appropriate acupuncture treatment schedule for chronic pain. METHODS: Embase, Pubmed, Cochrane Central Register of Controlled Trials, and reference lists were searched from 2009 to 2018 to identify randomized controlled trials of acupuncture for chronic pain conditions. We collected factors of treatment schedule (D, duration of each treatment session; N, number of treatment sessions; T, total duration of treatment in weeks) from each of the trials, and the linear regression analysis with real pain relief rate (both treatment and follow-up) was performed. Furthermore, we recommend the concept of "DOSE" and frequency (F) to evaluate the dose and frequency effect of acupuncture. RESULTS: Twenty-four trials with a total number of 3461 patients met the inclusion criteria. Of these, data from 23 studies were available for analysis. Firstly, the results showed that follow-up pain relief rate was decreased slightly with the increase of the duration of each session and DOSE (r=-0.3414 and r=-0.3246, respectively), but those two factors had no correlation with the pain relief rate after treatment. Secondly, it showed that either lower frequency with 2 sessions/week and higher frequency greater than 2 sessions/week or DOSE of 30 mins/week can achieve higher pain relief rate after treatment. Thirdly, we found the rate of pain relief remained at a high level greater than 20% up to 18 weeks after the treatment, and then it dropped sharply below 10% with the follow-up extended. A positive relationship was found between study score and pain relief both in treatment and follow-up (r=0.4654 and r=0.3046, respectively). CONCLUSIONS: The effect of acupuncture varies greatly with the different schedules of acupuncture, so it is necessary to review and choose the appropriate schedule. Although the current work is based on a limited number of trials, the findings suggest that acupuncture has a dose and frequency effect presenting within a certain range, which would have considerable implications for the design and interpretation of clinical trials. More high-quality randomized controlled trials on acupuncture schedule research were needed for providing more definitive evidence.