Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation

Introduction. The exchange protein directly activated by cAMP (Epac1), a downstream target of the second messenger cAMP, modulates multiple biological effects of cAMP, alone or in cooperation with protein kinase A (PKC). Epac1 is necessary for promoting protein kinase C (PKC) translocation and activation. The aim of the study was to assess the intensity of Epac1 and protein kinase C (PKC) immunoreactivity in lung cancer and para-carcinoma tissues, and their associations with clinical-pathological indexes. Correlations between the immunoreactivity of Epac1, PKC, A-kinase anchor protein 95 (AKAP95) and connexin43 (Cx43) were also examined. Material and methods. Epac1, Cx43 (46 cases) and PKC, AKAP95 (45 cases) immunoexpression levels were determined in tissue samples of lung cancer and in 12 samples of neighboring para-carcinoma specimens by the PV-9000 Two-step immunohistochemical technique. Results. The percentage of Epac1 positive samples was significantly lower in lung cancer tissue than in neighboring para-carcinoma specimens (37% vs. 83.3%, p < 0.05); the difference in PKC immunoreactivity was not significant (64.4% vs. 91.7%). Epac1 expression was associated with the degree of malignancy and lymph node metastasis (P < 0.05), but not with histological type (P > 0.05), whereas PKC expression was not related to these parameters. Interestingly, Epac1 expression was correlated with PKC and Cx43 expression. Moreover, PKC expression was correlated with AKAP95 expression. Conclusion. Normal Epac1 expression may suppress lung cancer occurrence and metastasis, and its downregulation is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation.

Tai Chi for the prophylaxis of episodic migraine: protocol of a non-inferiority randomized controlled trial with mechanism exploration

Abstract Background Migraine is a complex neurovascular disorder with considerable clinical, social and economic issues. Tai chi has the potential to be an alternative prophylactic treatment for migraine with high safety since the adverse effects and limited efficacy of available medications. Aims The proposed study aims to compare the prophylaxis efficacy of 24-week Tai Chi training on migraine attacks with the standard prophylactic medication; and to explore the mechanism of Tai Chi in preventing migraine attacks by analyzing the associations between changes of migraine attacks and changes of neurovascular functions and inflammatory makers. Method This is a two-arm parallel non-inferiority randomized controlled trial. In total 220 Hong Kong Chinese women aged 18–65 years with diagnosis of episodic migraine will be recruited and randomized to either the Tai Chi training group or the standard prophylactic medication group with 1:1 ratio, and receive the 24 weeks of modified 33-short form Yang-style Tai Chi training and the standard prophylactic medications, respectively. A 24-week follow-up will be implemented for both groups. For efficacy examination, the primary outcome was the frequency of migraine attacks measured by the migraine diary; and for the mechanism exploration, the primary outcome was the volume and number of white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). The measurements will be conducted at the baseline, 24th weeks, and 48th weeks. Linear mixed model will be adopted to comprehensively analyze the changes of variables within and between groups. Discussion Given the importance of reducing disease burden and financial cost of migraine attacks, the findings of this study will provide new insights regarding the role of Tai Chi in alleviating migraine burden and further shed light on the mechanism action of Tai Chi on preventing headache attacks. Trial registration ClinicalTrials.gov NCT05690737. Registered on January 28, 2023

Efficacy and feasibility of a 12-week Tai Chi training for the prophylaxis of episodic migraine in Hong Kong Chinese women: A randomized controlled trial

BackgroundTai Chi has been broadly applied as alternative treatment for many neurological and psychological disorders. Whereas no study using Tai Chi as prophylactic treatment for migraine. The purpose of this study was to preliminarily examine the efficacy and feasibility of a 12-week Tai Chi training on migraine attack prevention in a sample of Chinese women.MethodsA two-arm randomized controlled trial was designed. Women aged 18 to 65 years and diagnosed with episodic migraine were randomized to either Tai Chi group (TC group) or the waiting list control group. A modified 33-short form Yang-style Tai Chi training with 1 h per day, 5 days per week for 12 weeks was implemented in the TC group, with a 12-week follow up period. The control group received a “delayed” Tai Chi training at the end of the trial. The primary outcome was the differences in attack frequency between 4 weeks before baseline and at the 9–12 weeks after randomization. The intensity and duration of headache were also measured. The feasibility was evaluated by the maintenance of Tai Chi practice and satisfactory level of the participants toward training.ResultsEighty-two women were randomized, finally 40 in TC group and 33 in control group were involved in the analysis. On average, women in TC group had 3.0 times (95% CI: −4.0 to −2.0, P < 0.01) and 3.6 days (95% CI: −4.7 to −2.5, P < 0.01) reduction of migraine attack per month. Compared with the control group, the differences were statistically significant (−3.7 attacks/month, 95% CI: −5.4 to −1.9; and −3.0 migraine days/month, 95% CI: −4.5 to −1.5; both P < 0.001). The intensity and duration of headache had 0.6 (95% CI: −1.2 to −0.0, P < 0.05) units and 1.2 (IQR: −5.0 to 1.1, P < 0.05) hours reduction in TC group, respectively. Most of the participants (69.2%−97.4%) were satisfied with the training. At the end of 24 weeks, on average, the participants maintained 1.5 times of practice per week and 20 min for each practice.ConclusionThe 12-week Tai Chi training significantly decreased the frequency of migraine attack. It was acceptable and practicable among female migraineurs.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT03015753