Remote ischemic post-conditioning protects against myocardial ischemia/reperfusion injury by inhibiting the Rho-kinase signaling pathway.

The aim of the present study was to observe the effect of Rho-kinase on remote ischemic post-conditioning (RIPostC) and explore the underlying mechanisms. Male Sprague Dawley rats (n=32) were randomly distributed into four groups: Sham group, ischemia/reperfusion (I/R) group, RIPostC group and I/R with fasudil group (I/R+Fas). Infarction size was detected by triphenyltetrazolium chloride staining. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) and cardiac troponin I (cTnI) were measured using an ultraviolet spectrophotometer. The mRNA expression levels of Rho-associated coiled-coil containing protein kinase (ROCK)-1 and ROCK2, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected via reverse transcription-PCR. The protein expression levels of phosphorylated-myosin phosphatase target subunit (p-MYPT1) and phosphorylated-myosin light chain (p-MLC) were assessed by western blotting. The results demonstrated that RIPostC could decrease the infarct size, the levels of CK, LDH, cTnI and MDA and increase the activity of SOD compared with the I/R group. In addition, the mRNA expression of ROCK1 and ROCK2 was downregulated, the protein expression of p-MYPT1 and p-MLC was decreased, and the ratio of Bcl-2/Bax was elevated in the RIPostC groups compared with the I/R group. Notably, the aforementioned index in I/R with Fas group was similar to the RIPostC group and no significant difference was observed between RIPostC and I/R+Fas. These results revealed that RIPostC could attenuate I/R injury and the underlying mechanisms might be associated with a reduction in myocardial apoptosis and the suppression of the Rho-kinase signaling pathway.

The Protective Effect of Low-Dose Ethanol on Myocardial Fibrosis through Downregulating the JNK Signaling Pathway in Diabetic Rats.

Objective. To investigate the effects of low dose ethanol feeding in diabetic rats and analyze its underlying mechanisms. Methods. Male Sprague-Dawley rats were divided into 4 groups: control (Con), diabetes at 4 weeks (DM4W), diabetes at 8 weeks (DM8W), and EtOH + DM8W. After 8 weeks, hemodynamic parameters were recorded and heart weight/body weight (H/B) and hydroxyproline (Hp) content in myocardium were measured. Morphology of collagen in myocardial tissue was observed with Masson's trichrome staining method and collagen volume fraction (CVF) was analysed. The mRNA expression of ALDH2 was assessed with Real-Time PCR. The protein expressions of p-JNK and JNK were evaluated using western blot. Results. In contrast to Con group, there was no difference in hemodynamic parameters in DM4W group, but mean arterial pressure and heart rate were decreased in DM8W group, and the ratios of H/B, Hp, and CVF were markedly increased. ALDH2 mRNA expression was decreased, while the ratio of p-JNK/JNK were increased. Compared with DM8W group, the above indexes were improved in EtOH + DM8W group. Conclusion. With low dose ethanol intervention, enhanced ALDH2 expression can antagonize the happening of myocardial fibrosis in diabetic rats, which may be relevant with downregulating the JNK pathway.

Stomach cancer mortality among workers exposed to asbestos: a meta-analysis.

BACKGROUND: The relationship between asbestos and stomach cancer is not well understood because of small number of cases. This study aimed to determine the incidence and mortality of stomach cancer among workers exposed to asbestos based on a systematic review and meta-analysis approach. METHODS: Relevant English electronic databases were systematically searched for published studies characterizing the risk of developing stomach cancer as a result of asbestos exposure. Standardized mortality rate (SMR) for stomach cancer with its 95% confidence interval (CI) was pooled using a fixed-/random-effect model in STATA. RESULTS: A total of 32 independent studies were included for the analysis. The overall SMR for stomach cancer was 1.19 (95% CI 1.06-1.34), with a moderate degree of heterogeneity across the studies (I(2) = 37.6%, P = 0.011). Being male, exposure to crocidolite, miners, studies conducted in Europe and Oceania, and long study follow-up (≥ 25 years) all contribute to significantly higher SMR. Significant publication bias was observed. CONCLUSION: Elevated risk of stomach cancer mortality was evidenced among workers exposed to crocidolite, especially male miners.

Remote ischemic postconditioning protects the heart by upregulating ALDH2 expression levels through the PI3K/Akt signaling pathway.

Remote ischemic postconditioning (RIPostC) has been demonstrated to protect the myocardium against ischemia/reperfusion (I/R) injury; however, the mediator and underlying mechanisms remain to be elucidated. It has been confirmed that aldehyde dehydrogenase 2 (ALDH2) is involved in the remote ischemic preconditioning pathway, but whether it is involved in RIPostC remains unknown. The aim of the present study was to determine whether increased ALDH2 expression levels were involved in the cardioprotective effect evoked by RIPostC via the phosphatidylinositol­3­kinase (PI3K)/Akt signaling pathway. Male Sprague Dawley rats (n=48) were randomly allocated into the following four groups: Sham group, I/R group, RIPostC group, and RIPostC plus wortmannin group (RIPostC+Wort). With the exception of the Sham group, the anesthetized rats underwent 45 min of coronary artery occlusion followed by 180 min of reperfusion to mimic an I/R injury model. Hemodynamic parameters, including the mean arterial pressure and heart rate, were recorded, the infarct size was determined and the plasma lactate dehydrogenase (LDH) content and creatine kinase (CK) activity levels were measured. The expression levels of Bcl­2 and Bax at the mRNA level and ALDH2, Akt, phospho­Akt (p­Akt), caspase­3 and cleaved caspase­3 at the protein level in the left anterior myocardium were assessed. In the RIPostC group, the infarct size was reduced versus that of the I/R group. The plasma LDH content and CK activity levels were also reduced. The expression levels of ALDH2 protein were elevated, accompanied with increases in the levels of Bcl­2/Bax and p­Akt/Akt and a reduction in the levels of cleaved caspase­3. When the PI3K inhibitor wortmannin was administered at reperfusion, the p­Akt/Akt ratio was markedly reduced and associated with a reduction in the ALDH2 and Bcl­2/Bax levels, and the cleaved caspase­3 expression levels were elevated. In conclusion, ALDH2 may be an important mediator in the cardioprotection of RIPostC through the PI3K/Akt­dependent signaling pathway.