Periostin, the distribution and expression of which were consistent with the extent of myocardial fibrosis, might be a potential biomarker of cardiac remodeling in heart failure patients.

Lung cancer is the most common malignancy and exhibits significant morbidity and mortality worldwide. Among all lung cancer subtypes, non-small-cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Although there have been intensive investigations on the underlying mechanism of NSCLC development and progression, the exact molecular basis is not well understood. Further insights on important molecular regulators of lung cancer are needed for development of novel therapeutics. The heat shock protein (HSP) family is a group of molecular chaperones that assist in protein folding, modification, and transportation. Different HSPs are essential for tumor cell survival by binding diverse client proteins and regulating homeostasis. In the current study, we sought to characterize HSP70 and HSP90 as potent regulators of NSCLC growth. Our results indicate that differential expression of HSP70 is associated with the malignant phenotype of NSCLC cell lines and plays an important regulatory role in NSCLC cell proliferation. Moreover, a specific inhibitor of HSP70, VER-155008 significantly inhibits NSCLC proliferation and cell cycle progression. We showed that this effect is largely abolished by HSP70 overexpression, indicating that the inhibitory effect of VER-155008 on cell growth is specifically through HSP70 inhibition. In addition, 17-AAD, an inhibitor of HSP90, exerts a potent synergistic effect on NSCLC proliferation with VER-155008. We also observed that inhibition of HSP70 by VER-155008 can sensitize A549 cells to ionizing radiation. These data provide proof-of-principle that VER-155008 can be a good candidate for NSCLC treatment and HSP machinery is a good target for developing NSCLC therapeutics.

H2S enhances AP-1 binding activity with the SIRT3 promoter, thereby upregulating SIRT3 expression and ultimately reducing oxidant-provoked vascular endothelial dysfunction. Antioxid. Redox Signal. 24, 329-343.

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AimIt is controversial that whether sleeve lobectomy (SL) should be promoted more worthy than pneumonectomy (PN) in suitable patients.MethodsWe searched all studies that had been published in English from PUBMED and Embase which compared the short-term and long-term outcomes of SL and pneumonectomy (PN) in patients with non-small cell lung cancer (NSCLC).ResultsNineteen studies met our criteria with a combined total of 3878 subjects, of which 1316 (33.9%) underwent SL and 2562 (66.1%) underwent PN. The odds ratio was 0.50 (95% CI: 0.34-0.72) for postoperative mortality, 1.17 (95% CI: 0.82-1.67) for postoperative complications, 0.78 (95% CI: 0.47-1.29) for locoregional recurrences. The risk difference for 1-, 3-, 5- year was 0.11 (95% CI: 0.07-0.14), 0.15 (95% CI: 0.06-0.24), 0.15 (95% CI: 0.09-0.20),respectively. The pooled hazard ratio was 0.63 (95% CI: 0.56-0.71) in favor of SL group.ConclusionSL is more worthy to be done than PN in suitable patients with less mortality and better long-term survival.

Hydrogen sulfide (H2S) is a gasotransmitter which regulates multiple cardiovascular functions. However, the precise roles of H2S in modulating myocardial fibrosis in vivo and cardiac fibroblast proliferation in vitro remain unclear. We investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial fibrosis. Spontaneously hypertensive rats (SHR) were administrated with GYY4137 by intraperitoneal injection daily for 4 weeks. GYY4137 decreased systolic blood pressure and inhibited myocardial fibrosis in SHR as evidenced by improved cardiac collagen volume fraction (CVF) in the left ventricle (LV), ratio of perivascular collagen area (PVCA) to lumen area (LA) in perivascular regions, reduced hydroxyproline concentration, collagen I and III mRNA expression, and cross-linked collagen. GYY4137 also inhibited angiotensin II- (Ang II-) induced neonatal rat cardiac fibroblast proliferation, reduced the number of fibroblasts in S phase, decreased collagen I and III mRNA expression and protein synthesis, attenuated oxidative stress, and suppressed α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) expression as well as Smad2 phosphorylation. These results indicate that GYY4137 improves myocardial fibrosis perhaps by a mechanism involving inhibition of oxidative stress, blockade of the TGF-β1/Smad2 signaling pathway, and decrease in α-SMA expression in cardiac fibroblasts.

BackgroundWe tested the hypothesis that direct renin inhibition with aliskiren protects against myocardial ischemia/reperfusion (I/R) injury in spontaneously hypertensive rats (SHR), and examined the mechanism by which this occurs.Methods and ResultsMale SHR were treated (orally, 4 weeks) with saline or aliskiren (30 or 60 mg kg−1 day−1) and subjected to 30 minutes of left anterior descending coronary artery occlusion followed by 6 or 24 hours of reperfusion. Only the higher dose significantly lowered systolic blood pressure, the lower dose causing a smaller apparent lowering that was nonsignificant. Despite this difference in blood pressure‐lowering effect, both doses increased the ejection fraction and fractional shortening and reduced myocardial infarct size equally. I/R decreased cardiac expression of phosphatidylinositol 3‐kinase (PI3K), phospho‐Akt and phospho‐endothelial nitric oxide synthase (phospho‐eNOS), but increased expression of inducible nitric oxide synthase (iNOS); these changes were all abrogated by aliskiren. Moreover, aliskiren decreased superoxide anion generation and increased cyclic guanosine‐3′,5′‐monophosphate, an index of bioactive nitric oxide, in myocardium. It also decreased the expression of myocardial matrix metalloproteinase‐2, matrix metalloproteinase‐9, and tissue inhibitor of metalloproteinases‐1 (TIMP‐1) following I/R. In a Langendorff heart preparation, the detrimental cardiac effects of I/R were abrogated by aliskiren, and these protective effects were abolished by NOS or PI3K inhibition. In a parallel study, although specific iNOS inhibition reduced plasma malondialdehyde and myocardial superoxide anion generation, it did not affect the deleterious effects of I/R on myocardial structure and function.ConclusionsDirect renin inhibition protects against myocardial I/R injury through activation of the PI3K‐Akt‐eNOS pathway.

Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.