Abstract-Protection by ischemic preconditioning is lost in cardiomyocytes and hearts of heterozygous connexin 43 deficient (Cx43 ϩ/Ϫ ) mice. Because connexin 43 (Cx43) is localized in cardiomyocyte mitochondria and mitochondrial Cx43 content is increased with ischemic preconditioning, we now tried to identify a functional defect at the level of the mitochondria in Cx43 ϩ/Ϫ mice by use of diazoxide and menadione. Diazoxide stimulates the mitochondrial formation of reactive oxygen species (ROS) and menadione generates superoxide at multiple intracellular sites; both substances elicit cardioprotection through increased ROS formation. ROS formation in response to the potassium ionophore valinomycin was also measured for comparison. Menadione (2 mol/L) and valinomycin (10 nmol/L) induced similar ROS formation in wild-type (WT) and Cx43 ϩ/Ϫ ) mice cannot be protected by ischemic preconditioning. 1,2 Isolated cardiomyocytes are also not protected by ischemic preconditioning, and loss of protection is therefore independent of gap junctions. 3 Most of the signaling pathways of ischemic preconditioning converge at the mitochondria 4 -6 and mitochondrial free radical formation mediates signal transduction through posttranslational modification of redox-sensitive proteins. 7,8 We have recently demonstrated the presence of Cx43 in the mitochondria and the increase of its mitochondrial content with ischemic preconditioning. 9 Now we attempted to define the functional role of Cx43 in the mitochondria by use of diazoxide, which stimulates the formation of reactive oxygen species (ROS). Diazoxide was compared with menadione, which generates superoxide at multiple intracellular sites caused by redox cycling reactions catalyzed by several flavoenzymes. 10 The cardioprotective effects elicited by diazoxide and menadione have been attributed to ROS formation. 7,8,11,12 ROS formation by diazoxide was also compared with that by valinomycin, which is a potassium ionophore 13 and assumed to induce ROS formation secondary to potassium influx into mitochondria and matrix swelling. 14 Materials and MethodsAll experiments were performed according to the guidelines of the American Physiological Society and approved by the local bioethical committee on animal experimentation. Western BlottingTotal cardiac Cx43 content was determined as described, 1 and the localization of Cx43 at the mitochondria was measured as the ratio of Cx43 to the adenine nucleotide transporter in isolated mitochondria of 6 WT and Cx43 ϩ/Ϫ each. 9Original In Vitro ExperimentsCardiomyocytes were isolated from Cx43 ϩ/Ϫ and WT mice, as previously described. 3 Simulated ischemia was induced by pelleting cardiomyocytes in hypoxic solution (pHϭ6.5), sealed with a layer of mineral oil. 3 Cardiomyocytes were incubated with diazoxide (200 or 500 mol/L) or menadione (2 mol/L) (Sigma Aldrich, Germany) for 30 minutes followed by 15 minutes wash-out before simulated ischemia. At 0, 60, and 120 minutes of simulated ischemia, aliquots from each group were subjected to simulated reper...

Serum adropin level was significantly lower in type 2 diabetic patients than in non-diabetic patients and was inversely and independently associated with angiographic severity of coronary atherosclerosis, suggesting that serum adropin serves as a novel predictor of coronary atherosclerosis.

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Objective-Both advanced glycosylation end products (AGEs) and dendritic cells (DCs) have been shown to play a causative role in atherosclerosis. However, whether they function interactively in the process remains uncertain. We therefore studied the effects of AGE-bovine serum albumin (AGE-BSA) on the maturation of DCs and the expressions of scavenger receptor-A (SR-A) and receptor for AGEs (RAGE) on DCs. Key Words: advanced glycosylation end products Ⅲ atherosclerosis Ⅲ dendritic cells Ⅲ immunity Ⅲ receptor for advanced glycosylation end products D iabetes is associated with severe atherosclerosis and cardiovascular diseases that account for a high mobility and mortality in industrialized countries. 1 It is therefore very important for us to understand the mechanisms of how the diseases occur. Advanced glycosylation end products (AGEs) (long-term products of the Maillard reaction) have been shown to play a causative role in diabetic vasculopathy and atherosclerosis. 2,3 In diabetic atherosclerotic lesions, not only the deposition of AGEs but also the colocalization of AGEs antigen and AGEs receptors (scavenger receptor A [SR-A], receptor for AGEs [RAGE]) were found. 2,3 Additionally, accumulating evidences have suggested that dendritic cells (DCs) also play a crucial role in atherosclerosis 4 by activating T-cell in atherosclerosis. 5 Proinflammatory factors can promote maturation of DCs corresponding to a switch from a phagocytic stage to a stage of strong T cell-stimulatory capacity. The interactive roles of AGEs and DCs remain unknown now. We therefore examined the effect of advanced glycosylation end-bovine serum albumin (AGE-BSA) on DCs maturation, cytokine secretion, and SR-A and RAGE expression. MethodsThe informed consent was obtained from all volunteers and the study protocol was approved by our institutional ethical committee.

ObjectivesEpidemiological studies aimed at stroke and its risk factors can help identify persons at higher risk and therefore promote stroke prevention strategies. We aimed to explore the current prevalence of stroke and its associated risk factors in northeast China.DesignPopulation based cross sectional study.SettingData were collected using a structured precoded questionnaire designed by the Stroke Screening and Prevention Programme of the National Health and Family Planning Commission of China, between January and March 2016.Participants4100 permanent residents, aged 40 years or older, who had lived in Dehui City of Jilin Province for more than 6 months volunteered to participate in the survey, with a response rate of 92.2%. For the purpose of the present analysis, 48 subjects were excluded due to missing values, giving a total of 4052 people included in this analysis.Main outcome measureThe questionnaire included demographic characteristics, stroke related behavioural factors, personal and family medical history of stroke, physical examination and laboratory testing.ResultsThe overall prevalence of stroke in Jilin Province was 7.2% (95% CI 6.3% to 8.2%). Of all stroke cases, 91.7% (95% CI 87.4% to 94.6%) were ischaemic stroke and 8.3% (95% CI 5.4% to 12.6%) were haemorrhagic stroke. The prevalence rates of dyslipidaemia, smoking and hypertension were ranked as the top three cerebrovascular risk factors and were 62.1%, 61.8% and 57.3%, respectively. We found that hypertension, dyslipidaemia and lack of exercise were associated with ischaemic stroke. However, only hypertension (OR=4.064, 95% CI 1.358 to 12.160) was significantly associated with haemorrhagic stroke.ConclusionsThe prevalence of stroke, especially ischaemic stroke, and associated cerebrovascular risk factors among adults aged 40 years or older in northeast China were high. A higher regional prevalence of hypertension, dyslipidaemia and lack of exercise may be responsible.

Connexin 43 (Cx43) is the predominant protein forming gap junctions and non-junctional hemichannels in ventricular myocardium, but Cx43 is also localized at the inner membrane of cardiomyocyte mitochondria. In cardiomyocytes, Cx43 is involved in the formation of reactive oxygen species, which are central to the signal transduction cascade of ischemic preconditioning's protection. Accordingly, genetically-induced or age-related loss of Cx43 abolishes infarct size reduction by ischemic preconditioning. Similarly, mitochondrial import inhibition of Cx43 completely blocks infarct size reduction by pharmacological preconditioning with diazoxide. In contrast to its importance for preconditioning-induced cardioprotection, Cx43 is not important for infarct size reduction by ischemic postconditioning. In summary, Cx43--especially Cx43 localized in mitochondria--appears to be one key element of the signal transduction cascade of the protection by preconditioning.

BackgroundDyslipidemia is an important independent modifiable risk factor for cardiovascular disease. The aim of this study was to explore the current prevalence, awareness, treatment and control of dyslipidemia and its associated influence factors in northeast China.MethodsIn this population-based cross-sectional study, we adopted a multi-stage, stratified sampling method to obtain a representative sample of 4052 permanent residents aged 40 years and over from different urban and rural regions in Dehui City of Jilin Province. All subjects completed a questionnaire and were examined for risk factors. Continuous data were presented as means ± standard deviations (SD) and compared using the Student’s t-test. Categorical variables were presented as proportions and compared using the Rao-Scott-χ 2 test in different subgroups. The associated influence factors for the prevalence, awareness, treatment and control of dyslipidemia were evaluated through multivariate logistic regression.ResultsThe prevalence of dyslipidemia was 62.1% overall, with 33.5, 43.9, 0.6, and 8.8% for high total cholesterol, triglyceride, low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol, respectively. Among those with dyslipidemia, the proportion of subjects who were aware, treated, and controlled was 14.4, 33.9, and 19.9%, respectively. Overweight or obesity (OR = 2.156; 95% CI: 1.863, 2.533), hypertension (OR = 1.643; 95% CI: 1.425, 1.893), or diabetes mellitus (OR = 2.173; 95% CI: 1.661, 2.844) increased the prevalence of dyslipidemia, also these participants were more likely to be aware of their condition, however, this did not increase the likelihood of treatment and control. Living in urban areas and higher education level also increased the awareness of dyslipidemia. Personal history of coronary heart disease was the strongest influence factors associated with better awareness, treatment and control of dyslipidemia. Overweight or obesity (OR = 0.404; 95% CI: 0.235, 0.695) and lack of exercise (OR = 0.423; 95% CI: 0.215, 0.830) were associated with poor control of dyslipidemia.ConclusionThe prevalence of dyslipidemia among adults aged 40 years and over in northeast China was high, however, the awareness, treatment, and control of dyslipidemia was measured at far from desirable levels. Renewed efforts taking influence factors into account are needed to improve the current unsatisfactory condition.

Resveratrol (3,4′,5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest group of oligomeric stilbenes. Resveratrol oligomers have multiple beneficial properties, of which some are superior in activity, stability, and selectivity compared with resveratrol. The complicated structures and diverse biological activities are of significant interest for drug research and development and may provide promising prospects as cancer preventive and therapeutical agents. This review presents an overview on preventive or anticancer properties of resveratrol oligomers.