Honokiol antagonizes doxorubicin­induced cardiomyocyte senescence by inhibiting TXNIP­mediated NLRP3 inflammasome activation.

Senescence of cardiomyocytes is considered a key factor for the occurrence of doxorubicin (Dox)­associated cardiomyopathy. The NOD­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome is reported to be involved in the process of cellular senescence. Furthermore, thioredoxin­interactive protein (TXNIP) is required for NLRP3 inflammasome activation and is considered to be a key component in the regulation of the pathogenesis of senescence. Studies have demonstrated that pretreatment with honokiol (Hnk) can alleviate Dox­induced cardiotoxicity. However, the impact of Hnk on cardiomyocyte senescence elicited by Dox and the underlying mechanisms remain unclear. The present study demonstrated that Hnk was able to prevent Dox­induced senescence of H9c2 cardiomyocytes, indicated by decreased senescence­associated ß­galactosidase (SA­ß­gal) staining, as well as decreased expression of p16INK4A and p21. Hnk also inhibited TXNIP expression and NLRP3 inflammasome activation in Dox­stimulated H9c2 cardiomyocytes. When TXNIP expression was enforced by adenovirus­mediated gene overexpression, the NLRP3 inflammasome was activated, which led to inhibition of the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox treatment. Furthermore, adenovirus­mediated TXNIP­silencing inhibited the NLRP3 inflammasome. Consistently, TXNIP knockdown enhanced the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox stimulation. In summary, Hnk was found to be effective in protecting cardiomyocytes against Dox­stimulated senescence. This protective effect was mediated via the inhibition of TXNIP expression and the subsequent suppression of the NLRP3 inflammasome. These results demonstrated that Hnk may be of value as a cardioprotective drug by inhibiting cardiomyocyte senescence.

Prognostic Value of Neutrophil to Lymphocyte Ratio for In-hospital Mortality in Elderly Patients with Acute Myocardial Infarction.

Coronary artery disease (CAD) is a multifactorial disease in which inflammation plays a central role. This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio (NLR), the Global Registry of Acute Coronary Events (GRACE) score with in-hospital mortality of elderly patients with acute myocardial infarction (AMI) in an attempt to explore the prognostic value of these indices for elderly AMI patients. One thousand consecutive CAD patients were divided into two groups based on age 60. The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records. The NLR and GRACE score were calculated. In the elderly (≥60 years), patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) had significantly higher NLR than did those with unstable angina (UA) and stable angina pectoris (SAP) (P<0.01). The NLR was considerably elevated in older AMI patients compared with their younger counterparts (<60 years) (P<0.05). In elderly AMI patients, the NLR was considerably higher in the high-risk group than in both the low-risk and medium-risk groups based on the GRACE score (P<0.05 and P<0.01, respectively), and the NLR was positively correlated with the GRACE score (r=0.322, P<0.001). Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group (P<0.05). By curve receiver operator characteristic curve (ROC) analysis, the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve (AUC) 0.771 and 0.787, respectively, P<0.001]. It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.

Nrf2 protects against diabetic dysfunction of endothelial progenitor cells via regulating cell senescence.

Diabetes is associated with an increased risk of cardiovascular disease. A decrease in the number and functionality of endothelial progenitor cells (EPCs) leads to reduced endothelial repair and the development of cardiovascular disease. The aim of the present study was to explore the effect and underlying mechanisms of nuclear factor erythroid 2­related factor 2 (Nrf2) on EPC dysfunction caused by diabetic mellitus. The biological functions of EPCs in streptozotocin­induced diabetic mice were evaluated, including migration, proliferation, angiogenesis and the secretion of vascular endothelial growth factor (VEGF), stromal­derived growth factor (SDF) and nitric oxide (NO). Oxidative stress levels in diabetic EPCs were also assessed by detecting intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). EPC senescence was evaluated by measuring p16 and b­gal expression and observing the senescence­associated secretory phenotype. In addition, the function of EPCs and level of oxidative stress were assessed following Nrf2 silencing or activation. Nrf2 silencing resulted in a decrease of EPC biological functions, accelerated cell senescence and increased oxidative stress, as indicated by ROS and MDA upregulation accompanied with decreased SOD activity. Furthermore, Nrf2 silencing inhibited migration, proliferation and secretion in EPCs, while it increased oxidative stress and cell senescence. Nrf2 activation protected diabetic EPCs against the effects of oxidative stress and cell senescence, ameliorating the biological dysfunction of EPCs derived from mice with diabetes. In conclusion, Nrf2 overexpression protected against oxidative stress­induced functional damage in EPCs derived from diabetic mice by regulating cell senescence.

[Comparison of effects of taizhi' an capsule and pravastatin on vascular endothelial function in senile patients with coronary heart disease].

OBJECTIVE: To explore the anti-atherosclerosis effect of Taizhi'an Capsule (TZA) for providing a theoretical base of its application in preventing coronary heart disease (CHD), by way of observing the effects of TZA and pravastatin (PVT) on vascular endothelial function in senile patients with CHD. METHODS: Seventy-eight Senile patients with CHD were randomly divided into the TZA group and the PVT group, 39 in each group. Changes of carotid arterial intima-media thickness (IMT) and brachial arterial endothelium dependent diastolic function (FMD) before and after treatment were observed by non-invasive ultrasound test technique, and levels of serum nitric oxide (NO) and plasma endothelin-1 (ET-1) were determined as well. RESULTS: After TAZ treatment, IMT decreased from 1.21 +/- 0.17 mm to 0.91 +/- 0.13 mm, FMD increased from 5.02 +/- 0.58% to 8.97 +/- 0.39%, ET-1 lowered from 95.93 +/- 19.41 ng/L to 49.35 +/- 53.27 ng/L, and NO enhanced from 42.56 +/- 14.12 mumol/L to 69.84 +/- 21.96 mumol/L; after PVT treatment, the corresponding changes were 1.25 +/- 0.21 mm to 0.88 +/- 0.32 mm, 4.90 +/- 0.37% to 8.12 +/- 0.25%, 89.35 +/- 10.02 ng/L to 47.96 +/- 11.05 ng/L and 51.71 +/- 9.39 mumol/L to 72.93 +/- 16.51 mumol/L, all the changes were statistically significant. CONCLUSION: TZA can obviously improve the vascular endothelial function in old patients with CHD, which has the anti-atherosclerosis effect similar to that of PVT.

[Effect of the purariae-isofiavones on estrogen level in normal and ovariectomized rats].

OBJECTIVE: To study the effect of purariae isoflavone on estrogen level in ovariectomized rats. METHOD: 80 rats were divided into four groups randomly, every group with 20 rats: 1. Control group; 2. Normal + purariae isoflavone group; 3. Ovariectomized group; 4. Ovariectomized + purariae isoflavone group. Estrogen level and gonadotropin-releasing hormone level of all rats were measured. RESULT: Thirty days after being ovariectomized, E2, E3 level was significantly lower than that of the first group(P < 0.05). But Testerone, FSH, LH, PRL and GH increased(P < 0.05). After being gastrogavaged with purariae-isolfavone for thirty days, Estrogen level and gonadotropin-relasing hormone level of the second group were significantly lower in various degree than those of normal control group (P < 0.05). But in ovariectomized rats, the estrogen level was recovered (P > 0.05). The gonadotropin-releasing hormone level was increased (P < 0.05). CONCLUSION: Purariae-isoflavone can increase estrogen level to normal in ovariectomized rats by way of increasing the level of gonadotropin-releasing hormone. In normal rats, it has anti-estrogen effect.