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Adverse remodeling after myocardial infarction (MI) result in heart failure and sudden cardiac death. Fibulin7 (FBLN7) is an adhesion protein excreted into the extracellular matrix that functions in multiple biological processes. However, whether and how FBLN7 affects post‐MI cardiac remodeling remains unclear. Here, the authors identify FBLN7 as a critical profibrotic regulator of adverse cardiac remodeling. They observe significantly upregulated serum FBLN7 levels in MI patients with left ventricular remodeling compared to those without MI. Microarray dataset analysis reveal FBLN7 is upregulated in human heart samples from patients with dilated and hypertrophic cardiomyopathy compared with non‐failing hearts. The authors demonstrate that FBLN7 deletion attenuated post‐MI cardiac remodeling, leading to better cardiac function and reduced myocardial fibrosis, whereas overexpression of FBLN7 results in the opposite effects. Mechanistically, FBLN7 binds to the epidermal growth factor receptor (EGFR) through its EGF‐like domain, together with the EGF‐like calcium‐binding domain, and induces EGFR autophosphorylation at tyrosine (Y) 1068 and Y1173, which activates downstream focal adhesion kinase/AKT signaling, thereby leading to fibroblast‐to‐myofibroblast transdifferentiation. In addition, FBLN7‐EGFR mediates this signal transduction, and the fibrotic response is effectively suppressed by the inhibition of EGFR activity. Taken together, FBLN7 plays an important role in cardiac remodeling and fibrosis after MI. [ABSTRACT FROM AUTHOR]

We report the fabrication of the AlV 3 O 9 nanoflowers, which is then used as cathode and anode materials for high-performance lithium ion batteries. The existence of Al 3+ in the vanadium oxygen interlayers reduces electrochemical impedance and improves lithium ion diffusion coefficient of aluminum vanadates, resulting in the enhanced electrochemical performance. Electrochemical measurements show that the AlV 3 O 9 nanoflowers demonstrate good electrochemical performance as cathode and anode materials. Specially, the anode performance of aluminum vanadate is evaluated for the first time. A high capacity of 843 mA h g −1 for second cycle at 100 mA g −1 is obtained for AlV 3 O 9 anode. Even cycled at 1000 mA g −1 , it can maintain a high capacity of 295 mA h g −1 up to 500 cycles. The good performance of AlV 3 O 9 nanoflowers may be ascribed to their 3D hierarchical structure and the conductivity improvement by the incorporation of aluminum ions. [ABSTRACT FROM AUTHOR]

Background and Objective: MicroRNA (miR)-499 rs3746444 polymorphisms may participate in the pathogenesis of autoimmune diseases, but the results remain conflicting. We further investigated this association using a meta-analysis. Methods: We conducted a retrieval of studies and obtained the eligible studies if they met inclusion criteria. Two researchers independently extracted the data from original articles. The genotype frequencies were analysed using Stata software. Results: We finally archived six eligible studies that included 1,118 cases and 1,673 controls. After pooling the data, the results indicated that homozygote TT had an overall association with autoimmune diseases (TC + CC vs. TT: odds ratio [OR] 1.31, 95 % CI 1.11-1.55, p = 0.001). The allele C, genotype TC and CC, may be associated with rheumatoid arthritis (RA) risks in Mediterranean populations (C vs. T: OR 2. 00, 95 % CI 1.37-2.91, p < 0.001; TC vs. CC + TT: OR 1.76, 95 % CI 1.27-2.44; p = 0.001; CC vs. TC + TT: OR 2.31, 95 % CI 1.24-4.27, p = 0.008; CC vs. TT: OR 2.92, 95 % CI 1.59-5.37 , p = 0.001; TC vs. TT: OR 1.98, 95 % CI 1.42-2.77). The genotype TT may decrease the risk of RA in Mediterranean populations (TC + CC vs. TT: OR 2.15, 95 % CI 1.57-2.94, p < 0.001) rather than in East Asians. Conclusions: This study suggested that miR-499 polymorphisms were associated with a significantly increased risk of RA in Mediterranean populations. [ABSTRACT FROM AUTHOR]

Context: Sunitinib (SU) is a multi-targeted tyrosine kinase inhibitor anticancer agent whose clinical use is often limited by cardiovascular complications. Trimetazidine (TMZ) is an anti-angina agent that has been demonstrated cardioprotective effects in numerous cardiovascular conditions, but its potential effects in SU-induced cardiotoxicity have not been investigated. Objective: This study investigates the effect of TMZ in sunitinib-induced cardiotoxicity in vivo and in vitro and molecular mechanisms. Materials and methods: Male 129S1/SvImJ mice were treated with vehicle, SU (40 mg/kg/d) or SU and TMZ (20 mg/kg/d) via oral gavage for 28 days, and cardiovascular functions and cardiac protein expressions were examined. H9c2 cardiomyocytes were treated with vehicle, SU (2–10 μM) or SU and TMZ (40–120 μM) for 48 h, and cell viability, apoptosis, autophagy, and protein expression was tested. Results: SU induces hypertension (systolic blood pressure [SBP] + 28.33 ± 5.00 mmHg) and left ventricular dysfunction (left ventricular ejection fraction [LVEF] − 11.16 ± 2.53%) in mice. In H9c2 cardiomyocytes, SU reduces cell viability (IC50 4.07 μM) and inhibits the AMPK/mTOR/autophagy pathway (p < 0.05). TMZ co-administration with SU reverses SU-induced cardiotoxicity in mice (SBP − 23.75 ± 4.69 mmHg, LVEF + 10.95 ± 3.317%), alleviates cell viability loss in H9c2 cardiomyocytes (p < 0.01) and activates the AMPK/mTOR/autophagy pathway in vivo (p < 0.001) and in vitro (p < 0.05). Discussion and conclusions: Our results suggest TMZ as a potential cardioprotective approach for cardiovascular complications during SU regimen, and potentially for cardiotoxicity of other anticancer chemotherapies associated with cardiomyocyte autophagic pathways. [ABSTRACT FROM AUTHOR]

Sunitinib malate is a multi-targeted tyrosine kinase inhibitor used extensively for treatment of human tumors. However, cardiovascular adverse effects of sunitinib limit its clinical use. It is pivotal to elucidate molecular targets that mediate sunitinib-induced cardiotoxicity. Sirtuin 3 (Sirt3) is an effective mitochondrial deacetylase that has been reported to regulate sensitivity of different types of cells to chemotherapies, but roles of Sirt3 in sunitinib-induced cardiotoxicity have not been investigated. In the present study, we established wild type, Sirt3-knockout, and Sirt3-overexpressing mouse models of sunitinib (40 mg kg−1 day−1 for 28 days)-induced cardiotoxicity and examined cardiovascular functions and pathological changes. We further cultured wild type, Sirt3-knockout, and Sirt3-overexpressing primary mouse cardiac pericytes and analyzed sunitinib (10 μMol for 48 h)-induced alterations in cellular viability, cell death processes, and molecular pathways. Our results show that sunitinib predominantly induced hypertension, left ventricular systolic dysfunction, and cardiac pericyte death accompanied with upregulation of Sirt3 in cardiac pericytes, and these cardiotoxicities were significantly attenuated in Sirt3-knockout mice, but aggravated in Sirt3-overexpressing mice. Mechanistically, sunitinib induced cardiac pericyte death through inhibition of GSTP1/JNK/autophagy pathway and Sirt3 interacted with and inhibited GSTP1, further inhibiting the pathway and aggravating sunitinib-induced pericyte death. Conclusively, we demonstrate that Sirt3 promotes sensitivity to sunitinib-induced cardiotoxicity via GSTP1/JNK/autophagy pathway. Our results suggest Sirt3 might be a potential target for developing cardioprotective therapies for sunitinib-receiving patients. [ABSTRACT FROM AUTHOR]

This study investigates the role of ranolazine in contrast-associated acute kidney injury (CA-AKI) and potential mechanisms. For in vivo studies, mouse models of CA-AKI and control mice were treated with ranolazine or vehicle. Blood urea nitrogen (BUN) and serum creatinine were detected by spectrophotometry. Anti-T-cell immunoglobulin and mucin domain 1 (TIM 1) and anti-lipocalin 2 antibody (LCN2) were detected by immunofluorescence. Hemodynamic parameters were detected via invasive blood pressure measurement and renal artery color doppler ultrasound, capillary density was measured by CD31 immunofluorescence, vascular permeability assay was performed by Evans blue dye. The expressions of oxidative stress and apoptotic markers were measured and analyzed by immunofluorescence and western blotting. For in vitro studies, intracellular calcium concentration of HUVECs was measured with Fluo 3-AM under confocal microscopy. Results show that compared with control mice, serum BUN, creatinine, TIM 1 and LCN2 levels were elevated in CA-AKI mice, but this effect was alleviated by ranolazine-pretreatment. Safe doses of ranolazine (less than 64 mg/kg) had no significant effect on overall blood pressure, but substantially improved renal perfusion, reduced contrast-induced microcirculation disturbance, improved renal capillary density and attenuated renal vascular permeability in ranolazine-pretreated CA-AKI mice. Mechanistically, ranolazine markedly down-regulated oxidative stress and apoptosis markers compared to CA-AKI mice. Intracellularly, ranolazine attenuated calcium overload in HUVECs. These results indicate that ranolazine alleviates CA-AKI through modulation of calcium independent oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Cu3V2O7(OH)2·2H2O materials have been synthesized by a facile hydrothermal route without any templates. The XRD results showed that the as-prepared materials are of high crystallinity and high purity. The Cu3V2O7(OH)2·2H2O material prepared at 190°C for 12h is composed of a large quantity of well-separated nanoparticles with the diameters ranging from 50nm to 200nm. The results of electrochemical measurement indicate that the Cu3V2O7(OH)2·2H2O material exhibits high initial discharge capacity and high-rate capability. A high specific discharge capacity of 544, 503, 475, 458 and 429mAhg−1 can be achieved at different current densities of 10, 20, 30, 50 and 100mAg−1, respectively. The superior electrochemical properties suggest that they are a promising cathode material for implantable cardioverter defibrillators (ICDs). [ABSTRACT FROM AUTHOR]