CaMKK2 alleviates myocardial ischemia/reperfusion injury by inhibiting oxidative stress and inflammation via the action on the AMPK-AKT-GSK-3ß/Nrf2 signaling cascade.

OBJECTIVE: Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) can regulate numerous biological processes and is implicated in diverse pathological processes. Yet its role in myocardial ischemia/reperfusion (MI/R) injury remains unknown. This project explored the possible functions and mechanisms of CaMKK2 in MI/R injury. METHODS: A rat model of MI/R in vivo was established using the left anterior descending coronary artery ligation method. Rat cardiomyocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to establish a cell model. Overexpression of CaMKK2 was achieved by infecting recombinant adeno-associated virus or adenovirus expressing CaMKK2. Real-time quantitative PCR, immunoblotting, TTC staining, TUNEL assay, ELISA, oxidative stress detection assays, flow cytometry, and CCK-8 assay were carried out. RESULTS: A decline in CaMKK2 levels was induced by MI/R in vivo or H/R in vitro. Up-modulation of CaMKK2 in rats ameliorated the cardiac injury evoked by MI/R injury accompanied by suppression of cardiac apoptosis, oxidative stress, and proinflammatory response. Rat cardiomyocytes with CaMKK2 overexpression were also protected from H/R damage by inhibiting apoptosis, oxidative stress, and proinflammatory response. CaMKK2 overexpression led to increased phosphorylation of AMPK, AKT, and GSK-3ß, and enhanced activation of Nrf2 under MI/R or H/R conditions. Inhibition of AMPK abolished CaMKK2-mediated Nrf2 activation and relevant cardioprotective effect. Restraint of Nrf2 also diminished CaMKK2-mediated relevant cardioprotective effect. CONCLUSIONS: Up-regulation of CaMKK2 provides a therapeutic benefit in the rat model of MI/R injury by boosting the Nrf2 pathway through regulation of AMPK/AKT/GSK-3ß, which suggests CaMKK2 as a new molecular target for the treatment of MI/R injury.

Using a mixed method to identify communication skills training priorities for Chinese general practitioners in diabetes care.

BACKGROUND: In China diabetes care is gradually shifting from secondary to primary care with great infrastructure investment and GP training. However, most GPs in China lack communication skills training, which is a huge obstacle in communication with their patients in primary care. In this study we seek to identify training priorities that is evidence-based, appropriate for the context of primary care in China, and that meet the real needs of both GPs and people with diabetes. METHODS: A mixed method approach was used. A conceptual framework was designed based on the MRC framework, action research and adult learning theories. Through a systematic review of the literature and qualitative research with GPs and patients with diabetes, a list of communication skills training components was developed by the research team. A modified nominal group technique (NGT) with GPs was used to evaluate these contents. Purposive sampling was used to recruit a variation of participants (age, work area, practice years and education background) from general practices in Guangzhou city, China. Eight structured nominal groups were facilitated to elicit the views of group members, and participants rated the 9-point Likert scale of importance and feasibility of the training items independently, before and after focus groups. The ranking of each item was calculated, based on the mean Likert score ratings from all participants. Video recordings of four NGT group discussions were thematically analysed using the Framework Method to explore reasons for any differences in rating items. RESULTS: 29 males and 29 female GPs from 28 general practices participated in NGT group discussions, with a mean age of 38.5 years and mean 12.3 years of practice experience. Based on the mean scores of importance and feasibility rating scores, the top 3 ranked priorities for communication training were 'health education' (importance 8.39, feasibility 7.67), 'discussing and explaining blood glucose monitoring' (8.31, 7.46), and 'diabetes complications and cardiovascular disease risk communication' (8.36, 7.12). Five main themes were identified from focus group discussions through qualitative analysis: 'impact on diabetes patients', 'GP attitudes towards communication skills', 'patient-related factors influencing the application of communication skills by GPs, 'local contextual factors', and 'training implementation'. CONCLUSIONS: Priorities for communication skills training for Chinese GPs in diabetes care were identified. These are set in the context of GPs' current experience of communication with patients in China who have diabetes, which is often unsatisfactory. This study describes the baseline from which better primary care for diabetes in China needs to be developed. Based on suggestions from GPs themselves, it identifies an agenda for improvement in communication as a key component of diabetes care in China.