This study aims to investigate and compare the effects of conventional breathing exercises and an inspiratory muscle training intervention on clinical symptoms in asthma patients. Sixty asthma patients (40–65 years old) were randomly assigned to either the conventional breathing exercises (BTE) or inspiratory muscle training (IMT) group for a 12-week intervention period. Outcome measurements were performed before and after the intervention, including the spirometry data, maximal inspiratory and expiratory pressures (PImax and PEmax), asthma control test, asthma control questionnaire, six-minute walk test, and three-day physical activity log, were recorded. PImax expressed as % of predicted value controlled for age and gender in healthy subjects (% predicted) increased by 16.92% (82.45% to 99.38%, p < 0.05) in the BTE group and by 29.84% (71.19% to 101.03%, p < 0.05) in the IMT group. Except for forced vital capacity, which was reduced in the BTE group, all other measured variables improved in both groups, and no statistically significant between-group differences were found. IMT appears to be more effective than breathing exercise intervention in promoting improvements in respiratory muscle strength. IMT may act as an alternative to conventional breathing exercises for middle-aged and elderly asthma patients.

Overtraining in athletes usually causes profound and lasting deleterious effects on the maintenance of health and exercise capacity. Here, we established an overtraining animal model to investigate the physiological modulation for future strategic applications in vivo. We subjected C57BL/6 mice to exhaustive treadmill exercises daily for 8 weeks (the exhaustive exercise group). Next, the physiological and psychological outcomes were compared with the regular exercise and sedentary groups. Outcome measures included growth, glucose tolerance, exercise metabolism profiles, cytokine levels, intestinal tight junction gene expression, and psychological behavioral changes. Our results revealed that overtraining negatively affected the physiological and psychological changes in the current model. The exhaustive exercise group exhibited significantly lower endurance performance and imbalanced energy expenditure, causing a decrease in body fat mass and slowing down the growth curve. In addition, the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) and immune cells (neutrophils and monocytes) were significantly elevated after successive exhaustive exercise interventions. Furthermore, overtraining-induced stress resulted in increased anxiety status and decreased food intake. Our findings reinforce the idea that an imbalance between exercise and recovery can impair health and performance maintenance after overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.

Immunosuppressant cyclosporine-A induces gingival hyperplasia, which is characterized by increased fibroblast proliferation and overproduction of extracellular matrix components and regulated by transforming growth factor-beta (TGF-β). The TGF-β and Sonic hedgehog (Shh) pathways both mediate cell proliferation. Crosstalk between these pathways in cancer has recently been proposed, but the hierarchical pattern of this crosstalk remains unclear. In normal fibroblasts, a TGF-β-stimulating Shh pattern was observed in induced fibrosis. However, Shh pathway involvement in cyclosporine-enhanced gingival proliferation and the existence of crosstalk with the TGF-β pathway remain unclear. Cyclosporine enhanced mRNA and protein levels of TGF-β and Shh in human gingival fibroblasts (RT-PCR and western blotting). A TGF-β pathway inhibitor mitigated cyclosporine-enhanced cell proliferation and an Shh pathway inhibitor attenuated cyclosporine-enhanced proliferation in fibroblasts (MTS assay and/or RT-PCR of PCNA). Exogenous TGF-β increased Shh expression; however, exogenous Shh did not alter TGF-β expression. The TGF-β pathway inhibitor mitigated cyclosporine-upregulated Shh expression, but the Shh pathway inhibitor did not alter cyclosporine-upregulated TGF-β expression. The TGF-β and Shh pathways mediate cyclosporine-enhanced gingival fibroblast proliferation. Exogenous TGF-β increased Shh expression, and inhibition of TGF-β signaling abrogated the cyclosporine-induced upregulation of Shh expression; however, TGF-β expression appeared unchanged by enhanced or inhibited Shh signaling. This is the first study demonstrating the role of Shh in cyclosporine-enhanced gingival cell proliferation; moreover, it defines a hierarchical crosstalk pattern in which TGF-β regulates Shh in gingival fibroblasts. Understanding the regulation of cyclosporine-related Shh and TGF-β signaling and crosstalk in gingival overgrowth will clarify the mechanism of cyclosporine-induced gingival enlargement and help develop targeted therapeutics for blocking these pathways, which can be applied in pre-clinical and clinical settings.

Background: Abnormal proliferation of vascular smooth muscle cells (VSMC) is a major cause of cardiovascular diseases (CVDs). Many studies suggest that vascular injury triggers VSMC dedifferentiation, which results in VSMC changes from a contractile to a synthetic phenotype; however, the underlying molecular mechanisms are still unclear.Methods: In this study, we examined how VSMC responds under mechanical stress by using time-course microarray data. A three-phase study was proposed to investigate the stress-induced differentially expressed genes (DEGs) in VSMC. First, DEGs were identified by using the moderated t-statistics test. Second, more DEGs were inferred by using the Gaussian Graphical Model (GGM). Finally, the topological parameters-based method and cluster analysis approach were employed to predict the last batch of DEGs. To identify the potential drugs for vascular diseases involve VSMC proliferation, the drug-gene interaction database, Connectivity Map (cMap) was employed. Success of the predictions were determined using in-vitro data, i.e. MTT and clonogenic assay.Results: Based on the differential expression calculation, at least 23 DEGs were found, and the findings were qualified by previous studies on VSMC. The results of gene set enrichment analysis indicated that the most often found enriched biological processes are cell-cycle-related processes. Furthermore, more stress-induced genes, well supported by literature, were found by applying graph theory to the gene association network (GAN). Finally, we showed that by processing the cMap input queries with a cluster algorithm, we achieved a substantial increase in the number of potential drugs with experimental IC50 measurements. With this novel approach, we have not only successfully identified the DEGs, but also improved the DEGs prediction by performing the topological and cluster analysis. Moreover, the findings are remarkably validated and in line with the literature. Furthermore, the cMap and DrugBank resources were used to identify potential drugs and targeted genes for vascular diseases involve VSMC proliferation. Our findings are supported by in-vitro experimental IC50, binding activity data and clinical trials.Conclusion: This study provides a systematic strategy to discover potential drugs and target genes, by which we hope to shed light on the treatments of VSMC proliferation associated diseases.