Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling.

Obesity is an important independent risk factor for cardiovascular diseases, remaining an important health concern worldwide. Evidence shows that saturated fatty acid-induced inflammation in cardiomyocytes contributes to obesity-related cardiomyopathy. Dapagliflozin (Dapa), a selective SGLT2 inhibitor, exerts a favorable preventive activity in heart failure. In this study, we investigated the protective effect of Dapa against cardiomyopathy caused by high fat diet-induced obesity in vitro and in vivo. Cultured rat cardiomyocyte H9c2 cells were pretreated with Dapa (1, 2.5 µM) for 1.5 h, followed by treatment with palmitic acid (PA, 200 µM) for 24 h. We showed that Dapa pretreatment concentration-dependently attenuated PA-induced cell hypertrophy, fibrosis and apoptosis. Transcriptome analysis revealed that inhibition of PA-activated MAPK/AP-1 pathway contributed to the protective effect of Dapa in H9c2 cells, and this was confirmed by anti-p-cJUN fluorescence staining assay. Using surface plasmon resonance analysis we found the direct binding of Dapa with NHE1. Gain and loss of function experiments further demonstrated the role of NHE1 in the protection of Dapa. In vivo experiments were conducted in mice fed a high fat diet for 5 months. The mice were administered Dapa (1 mg·kg-1·d-1, i.g.) in the last 2 months. Dapa administration significantly reduced the body weight and improved the serum lipid profiles. Dapa administration also alleviated HFD-induced cardiac dysfunction and cardiac aberrant remodeling via inhibiting MAPK/AP-1 pathway and ameliorating cardiac inflammation. In conclusion, Dapa exerts a direct protective effect against saturated fatty acid-induced cardiomyocyte injury in addition to the lowering effect on serum lipids. The protective effect results from negative regulating MAPK/AP-1 pathway in a NHE1-dependent way. The current study highlights the potential of clinical use of Dapa in the prevention of obesity-related cardiac dysfunction.

Effectiveness of E-SBIRT intervention in community healthcare institution in China: study proposal for a randomised controlled trial.

BACKGROUND: Many studies have demonstrated the effectiveness of Screening, Brief Intervention and Referral to Treatment (SBIRT) in addressing substance use problem. However, owing to the shortage of counsellors, it has not been widely used in China. With the development of smart medicine, we developed a web-based electronic SBIRT (E-SBIRT) program and explored the effectiveness of E-SBIRT in reducing substance use in China. METHODS: A randomised controlled trial will be conducted in primary healthcare institutions. Four primary healthcare institutions will be selected and randomly divided into an intervention group and a control group (each institution will recruit 60 participants, and in total, 240 participants will be recruited). The control group will get a pamphlet of drug abuse prevention, and the intervention group will get the E-SBIRT intervention and the pamphlet. Both groups will receive baseline and follow-up assessment at 1 and 3 months after the intervention. The primary outcome is the change in scores on the Alcohol, Smoking and Substance Use Involvement Screening Test, and the secondary outcomes include changes in motivation, depression, anxiety, positive/negative emotion, self-esteem, addiction knowledge and addiction severity index. CONCLUSIONS: If the 'E-SBIRT' program is found to be effective, it will be an accessible, affordable and widely implementable intervention to help participants at moderate risk of substance use to reduce their consumption. The potential benefit is to provide early intervention to high-risk patients in time and reduce the harmful consequences to individuals and society. TRIAL REGISTRATION NUMBER: NCT03452241.

The Effect of Intermittent Theta Burst Stimulation (iTBS) in Patients With Alcohol Use Disorder: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation technique which has a treatment potential for alcohol use disorder. Intermittent theta burst stimulation (iTBS) is a new rTMS technique which is shorter in duration and thus with better tolerability and shows similar efficacy as rTMS for the treatment of depression. The effect of iTBS on reducing craving in alcohol use disorder patients requires further investigation. METHODS: A randomized, controlled, single-blind, multicenter study with 60 alcohol use disorder patients randomized (2:1) to the iTBS group or the control group (sham iTBS). The stimulation target will be identical in the left dorsolateral prefrontal cortex (DLPFC). Baseline evaluations will be occurred before the intervention, after the intervention immediately, and 1 and 3 months after the intervention. The primary outcome of the study will be decrease of visual analogue scale (VAS) scores from baseline to the end of treatment. DISCUSSION: This study is a randomized controlled trial to investigate the efficacy of left DLPFC iTBS in a population of alcohol use disorder patients, compared with sham iTBS. If it is effective for alcohol use disorder, it may provide a potential treatment which is tolerable, accessible, and clinical useful. CINICAL TRIAL REGISTRATION: This study is registered in the ClinicalTrials with trial number NCT03932149. Registered 17 April 2019.

The Influences of Impulsivity and Education Levels on Severity of Alcohol Dependence.

BACKGROUND: Impulsivity contributes to the severity of alcohol use disorder. The association is affected by expectation towards alcohol use, emotional regulation and self-control. Here we investigated the influences of self-reported impulsivity and levels of education on severity of alcohol dependence. METHOD: We retrospectively analyzed the basic demographic information, alcohol consumption state, education years, depression and anxiety state, Alcohol Use Disorder Identification Test (AUDIT) and Barrett Impulsivity Scales (BIS) from a group of 66 AUD patients. RESULT: Impulsivity significantly predicted alcohol dependence severity (R 2 = 0.069, F = 4.724, p = 0.034). In addition, education years served as a moderator in the relationship between impulsivity and alcohol dependence severity (ΔR2 = 0.059, F = 4.414, p = 0.040). CONCLUSION: Self-reported impulsivity affects the severity of alcohol dependence, which might be different in patients with different education levels.