17ß-estradiol activates SOX6 to balance the anabolism and catabolism via estrogen receptor 2 in chondrocyte.

We investigated the influence of 17ß-estradiol (17ß-E2) on cartilage extracellular matrix (ECM) homeostasis in postmenopausal women. We focused on the roles of estrogen receptors (ESR) and SOX6 in 17ß-E2-mediated stimulation of ECM metabolism during chondrocyte (CH) degeneration. We compared the expression of anabolic genes (collagen II and aggrecan) and catabolic genes (MMPs and TIMPs) in IL-1ß-induced CH degeneration in vitro, with and without 17ß-E2 supplementation. We separately silenced the SOX6, ESR1, and ESR2 genes in CHs to determine their impact on 17ß-E2 treatment. Additionally, we used Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and luciferase assays to investigate protein-DNA interactions within ESR2 and SOX6-promoter complexes. After three days of IL-1ß treatment, ESR1/2, SOX6, collagen II, aggrecan, and TIMP1/3 were decreased, while MMP3/9/13 were increased. The addition of 17ß-E2 partially reversed these effects, but silencing SOX6, ESR1, or ESR2 weakened the protective effects of 17ß-E2. Silencing ESR2, but not ESR1, abolished the upregulation of SOX6 induced by 17ß-E2. ESR2 was found to bind the SOX6 promoter and regulate SOX6 expression. 17ß-E2 upregulates SOX6 through ESR2 mediation, and the synergistic effect of 17ß-E2 and ESR2 on SOX6 balances ECM metabolism in CHs.

A multifunctional adsorbent based on 2,3-dimercaptosuccinic acid/dopamine-modified magnetic iron oxide nanoparticles for the removal of heavy-metal ions.

Overexploitation of nature by humans has led to an increasingly serious issue of heavy-metal water pollution. To reduce the threat of water pollution to humans and the environment, it is imperative to develop or improve the water treatment technology for heavy-metal-containing wastewater. Functionalized Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) have been widely used as effective adsorbents for the removal of heavy-metal ions from water owing to their high efficiency, low cost, selective adsorption ability, and recyclability. In this study, Fe3O4@DA-DMSA magnetic nanoparticles (FDDMs) were prepared by the functionalization of Fe3O4 MNPs with environmentally friendly dopamine (DA) and a heavy-metal detoxifying agent such as 2,3-dimercaptosuccinic acid (DMSA) for the efficient and rapid adsorption of Pb2+, Cu2+, and Cd2+, with maximum adsorption capacities of 187.62, 63.01, and 49.46 mg/g, respectively. FDDMs exhibited the best ability to remove Pb2+ with a maximum adsorption capacity than that of the most reported Fe3O4 MNP-related adsorbents. In actual wastewater and multi-component simulated water samples contaminated with Pb2+, Cu2+, and Cd2+, the as-prepared adsorbent maintained a good removal ability for Pb2+ with low influence by ionic strength and interfering ions, as well as exhibited an excellent selectivity. According to the results of batch experiments and X-ray photoelectron spectroscopy (XPS) analysis of the adsorbent before and after adsorption, the adsorption mechanism of the adsorbent for the removal of heavy-metal ions mainly involves coordination and ion exchange. In addition, the adsorbent exhibited a good regeneration performance. Therefore, FDDMs can be considered as a promising adsorbent for the treatment of heavy-metal wastewater.

Development and validation of prognostic index based on autophagy-related genes in patient with head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, accounting for almost 50% of all malignancies in developing nations. Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment. However, autophagy-related gene sets have rarely been analyzed in HNSCC. Hence, it is necessary to assess its clinical and pathological significance in a larger cohort of patients with HNSCC. The purpose of this study was to establish a novel autophagy-related prognostic marker for HNSCC. We screened 232 autophagy-related genes (ARGs) and identified 38 differentially expressed ARGs in The Cancer Genome Atlas (TCGA) cohorts. The prognosis-related ARGs signature, established using the univariate and multivariate Cox proportional regression models, consists of 10 ARGs that could divide patients into high-risk and low-risk groups. Survival analysis indicated that patients in the high-risk group had dramatically shorter overall survival compared with their low-risk counterparts. Cox regression analysis further confirmed the independent prognostic value of the autophagy-related signature, and the area under the receiver operating characteristic curve of the combined prognostic model was 0.722. Finally, the efficacy of autophagy-related signature was also validated by an independent cohort from the Gene Expression Omnibus (GEO) database. Collectively, we successfully constructed a novel autophagy-related signature for the prediction of prognosis in patients with HNSCC.

Identification of LncRNA Prognostic Markers for Ovarian Cancer by Integration of Co-expression and CeRNA Network.

BACKGROUND: Ovarian cancer (OC), one of the most prevalent gynecological malignancies, is characterized by late detection and dismal prognosis. Recent studies show that long non-coding RNAs (lncRNAs) in competitive endogenous RNA (ceRNA) networks influence immune infiltration and cancer prognosis. However, the function of lncRNA in OC immune infiltration and prognosis remains unclear. METHODS: Transcriptomes of 378 OC samples and clinical data were retrieved from the TCGA repository. Modules related to immune cells were identified using weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis and survival analysis were then performed for the identification of immune-related lncRNAs in the brown module using Cox regression model. Finally, a ceRNA network was constructed by using the lncRNAs and mRNAs from the brown module. RESULTS: We found lncRNAs and mRNAs in the brown module to be significantly associated with immune cells in OC and identified 4 lncRNAs as potential OC prognostic markers. We further established that lncRNAs in the ceRNA network influence OC immune infiltration and prognosis by regulating miRNA, ultimately modulating mRNA levels. CONCLUSION: We have identified 4 lncRNAs as independent immune prognostic factors for OC. Furthermore, our findings offer novel insight into lncRNAs as OC immune and prognostic biomarkers.

Highly efficient and selective membrane separation of copper from nickel in ammoniacal solution using mixtures of M5640 and BESO as membrane carriers.

Separation of copper from nickel in ammoniacal/ammonium chloride solution using a flat-sheet supported liquid membrane impregnated with mixtures of Acorga M5640 and bis(2-ethylhexyl)sulfoxide (BESO) was investigated. The crucial parameters influencing copper transport and separation abilities of copper and nickel, such as carrier concentration of M5640 and BESO in the membrane phase, initial concentration of ions in the feed phase, H2SO4 concentration in the strip phase and membrane stability, were discussed. The results show that the mixtures of carriers (20 vol% M5640 + 20 vol% BESO) in the membrane have a considerable antagonistic effect on membrane transport of nickel, but favor copper transport. Nearly all of the copper was transferred from the feed phase to the strip phase after 12 hours with a flux of 2.05 × 10-5 mol m-2 s-1 under the following conditions: 100 mg L-1 each of the copper and nickel dissolved in 1.0 mol L-1 each of ammonia and ammonium chloride solution as the feed phase, 60 g L-1 H2SO4 as the strip phase, and stirring speed of 800 rpm in two aqueous phases. Meanwhile less than 3.8% of the nickel was transported into the strip phase over the same time. Copper and nickel were efficiently separated with a calculated factor of 26.3. Furthermore, satisfactory membrane stability was obtained with at least ten cycle runs in this separation system.

Wnt11 preserves mitochondrial membrane potential and protects cardiomyocytes against hypoxia through paracrine signaling.

We investigated the effect of Wnt11 on mitochondrial membrane integrity in cardiomyocytes (CMs) and the underlying mechanism of Wnt11-mediated CM protection against hypoxic injury. A rat mesenchymal stem cell (MSC) line that overexpresses Wnt11 (MSCWnt11 ) and a control cell line transduced with empty vector (MSCNull ) were established to determine the cardioprotective role of Wnt11 in response to hypoxia. Mitochondrial membrane integrity in MSCWnt11 cells was assessed using fluorescence assays. The role of paracrine signaling mediated by vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), and insulin-like growth factor 1 (IGF-1) in protecting CMs against hypoxia were investigated using cocultures of primary CMs from neonatal rats with conditioned medium (CdM) from MSCWnt11 . MSCWnt11 cells exposed to hypoxia reduced lactate dehydrogenase release from CMs and increased CM survival under hypoxia. In addition, CMs cocultured with CdM that were exposed to hypoxia showed reduced CM apoptosis and necrosis. There was significantly higher VEGF and IGF-1 release in the MSCWnt11 group compared with the MSCNull group, and the addition of anti-VEGF and anti-IGF-1 antibodies inhibited secretion. Moreover, mitochondrial membrane integrity was maintained in the MSCWnt11 cell line. In conclusion, overexpression of Wnt11 in MSCs promotes IGF-1 and VEGF release, thereby protecting CMs against hypoxia.

Adsorption of Cadmium Ions from an Aqueous Solution on a Highly Stable Dopamine-Modified Magnetic Nano-Adsorbent.

Magnetic nanomaterials were functionalized with dopamine hydrochloride as the functional reagent to afford a core-shell-type Fe3O4 modified with polydopamine (Fe3O4@PDA) composite, which was used for the adsorption of cadmium ions from an aqueous solution. In addition, the effects of environmental factors on the adsorption capacity were investigated. Furthermore, the adsorption kinetics, isotherm, and thermodynamics of the adsorbents were discussed. Results revealed that the adsorption of cadmium by Fe3O4@PDA reaches equilibrium within 120 min, and kinetic fitting data are consistent with the pseudo-second-order kinetics (R2 > 0.999). The adsorption isotherm of Cd2+ on Fe3O4@PDA was in agreement with the Freundlich model, with the maximum adsorption capacity of 21.58 mg/g. The thermodynamic parameters revealed that adsorption is inherently endothermic and spontaneous. Results obtained from the adsorption-desorption cycles revealed that Fe3O4@PDA exhibits ultra-high adsorption stability and reusability. Furthermore, the adsorbents were easily separated from water under an enhanced external magnetic field after adsorption due to the introduction of an iron-based core. Hence, this study demonstrates a promising magnetic nano-adsorbent for the effective removal of cadmium from cadmium-containing wastewater.

Regulation mechanism of aquaporin 9 gene on inflammatory response and cardiac function in rats with myocardial infarction through extracellular signal-regulated kinase1/2 pathway.

The aim of this study was to investigate the regulation mechanism of aquaporin 9 (AQP9) gene on inflammatory response and cardiac function in rats with myocardial infarction (MI) through extracellular signal-regulated kinase1/2 (ERK1/2) pathway. The constructed rats models of MI were randomly divided into 6 groups: control group (sham operation group, MI modeling sham operation), model group (MI modeling), NC group (MI modeling, tail vein injection of AQP9 negative control sequence vector), AQP9 shRNA group (MI modeling, tail vein injection of AQP9 shRNA plasmid vector), U0126 group (MI modeling, tail vein injection of ERK signaling pathway inhibitor), and AQP9 shRNA + U0126 group. The hemodynamics and cardiac function of rats in each group were detected on the seventh day of modeling. The levels of AQP9 and inflammatory factors [tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10)] in peripheral blood of rats were detected by ELISA method. qRT-PCR and western blot were used to detect the mRNA and protein expression of AQP9, ERK1/2, B-cell lymphoma-2 (Bcl-2), Bcl-associated x (Bax) in the myocardial tissue of rats. TTC and TUNEL staining were used to observe myocardial infarct size and apoptosis of myocardial cells in each group. Compared with control group, the levels of heart rate, left ventricular end-diastolic pressure, TNF-α, and IL-6 were increased in each group of rats with MI (all p < 0.05), while the levels of systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, and IL-10 were significantly decreased (all p < 0.05). The mRNA and protein expression levels of AQP9, ERK1/2 phosphorylation and Bax were significantly increased, as well as the myocardial infarct size, apoptosis index of myocardial tissue (all p < 0.05), the mRNA and protein expression levels of Bcl-2 were significantly decreased (all p < 0.05). The AQP9 gene knock-down or exogenous administration of the ERK1/2 inhibitor U0126 could improve the above indexes. However, the combination of AQP9 gene knock-down and U0126 showed no further effect. Silencing AQP9 gene can inhibit the activation of ERK1/2 signaling pathway, attenuate the inflammatory response in rats with MI, inhibit apoptosis of myocardial cells, and improve cardiac function.

Comparisons of efficacy, safety, and recurrence risk factors of paroxysmal and persistent atrial fibrillation catheter ablation using robotic magnetic navigation system.

BACKGROUND: No data exist on comparisons of efficacy, safety, and recurrence risk factors of paroxysmal and persistent atrial fibrillation (AF) ablation using robotic magnetic navigation system (MNS), respectively. METHODS: About 151 AF patients were prospectively enrolled and divided into paroxysmal AF group (n = 102) and persistent AF group (n = 49). Circumferential pulmonary vein antrum isolation (CPVI) was performed in all patients. Linear ablation at the left atrial roof and mitral isthmus was performed in patients with persistent AF in addition to CPVI. The procedural time, X-ray exposure time, acute and long-term success rates of CPVI, and procedure-related complications were analyzed. The AF recurrence rates in the two groups were compared during 1 year, and Cox regression was used to analyze the recurrence risk factors. RESULTS: The acute success rates of CPVI in the two groups were 98.04% and 97.96%, respectively. There were no significant differences in the procedural time, X-ray exposure time, and ablation time between the two groups (P > 0.05). No serious complications appeared in either group. The AF ablation success rates were 70.6% and 57.1% for the paroxysmal and persistent groups respectively at 12-month follow-up (P = 0.102). AF duration and coronary heart disease prior to ablation were associated with the higher AF recurrence in patients with persistent AF. CONCLUSION: Ablation using MNS is effective and safe both in patients with paroxysmal and persistent AF. AF duration and coronary heart disease prior to ablation are two independent risk factors of AF recurrence in patients with persistent AF postoperatively.

Effects of remote ischemic post-conditioning on platelet activation of AMI patients.

The recovery of ischemic myocardium blood perfusion is the main treatment option for acute myocardial infarction (AMI). However, this treatment option has multiple side effects that directly affect the quality of life of the patients. The activation of platelet function plays an important role in the occurrence, development and treatment of AMI. The aim of the present study was to analyze the effects of remote ischemic post-conditioning on platelet activation of AMI patients with primary PCI treatment and clinical prognosis. A total of 71 patients with AMI were treated with primary percutaneous coronary intervention (PCI). They were randomly divided into control group (n=34) and observation group (n=37). The patients in the observation group were treated with remote ischemic post-conditioning. Further, flow cytometer was used to detect the platelet alpha granule membrane glycoprotein (CD62P) and the percentages of activated IIb/IIIa (PAC-1). The maximum platelet aggregation rate induced by adenosine diphosphate (ADP) and arachidonic acid (AA) was measured by light transmittance aggrometer. The incidence of major adverse cardiac events (MACE) was compared between the two groups during the follow-up period of 6 months. The percentage of CD62P (24 h after PCI) in the observation group was significantly lower than control group (P<0.05). Further, the incidence of MACE in the observation group was also lower than that of the control group (P<0.05). Remote ischemic post-conditioning could reduce the incidence of MACE in patients with AMI after primary PCI treatment. Moreover, the above observation may be related to the improvement of platelet CD62P activation.

Comparison of the Effects of Ticagrelor and Clopidogrel on Inflammatory Factors, Vascular Endothelium Functions and Short-Term Prognosis in Patients with Acute ST-Segment Elevation Myocardial Infarction Undergoing Emergency Percutaneous Coronary Intervention: a Pilot Study.

BACKGROUND/AIMS: Acute ST-segment elevation of myocardial infarction (STEMI) is the most severe type of acute coronary syndrome (ACS). Particular attention has been focused on studying the pathogenesis of STEMI, and how to prevent thrombosis, reduce inflammatory reaction, stabilize plaques and improve vascular endothelial functions to preserve the survived myocardium. This study aimed to compare the anti-inflammatory endothelium-protective effects, clinical prognosis, and relevant bleeding risks of ticagrelor versus clopidogrel in patients with STEMI who underwent urgent percutaneous coronary intervention (PCI) and provide certain experimental evidence and a theoretical basis for the selection of safe and effective drugs and their proper dosage, thereby further guiding clinical medication. METHODS: We sequentially enrolled 193 patients (104 males and 89 females) admitted to hospital due to acute STEMI. These patients underwent urgent PCI between December 2013 and May 2015 and met the inclusion criteria. They were assigned (1: 1) into two groups according to different treatments, 97 patients in the ticagrelor group (treatment group), and 96 patients in the clopidogrel group (control group). Levels of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and endothelial cell-specific molecule 1 (ESM-1) taken at admission and 24 h, 4 days, and 7 days after administration, as well as the correlation between the levels of IL-6, hs-CRP, and ESM-1, were determined in the two groups. At the same time, the effects of treatment with ticagrelor and clopidogrel on the efficacy endpoint events (ischemic and safety) were explored. RESULTS: No statistically significant difference was found in the levels of hs-CRP, IL-6, or ESM-1 at admission between the two groups (P> 0.05); Their levels were significantly elevated 24 h after administration, with statistical differences between two groups (P< 0.05). Furthermore, a downward trend with statistically significant differences was found on Day 4 and Day 7 (P< 0.05); ESM-1 levels increased along with increases of hs-CRP and IL-6 levels, indicating ESM-1 was positively correlated with hs-CRP (r=0.523, P< 0.001) and IL-6 (r=0.431, P< 0.001); and the occurrence rates of ischemic endpoint events at 30 days were lower in the treatment group than in the control group. The occurrence of safety endpoint events was higher than in the control group; however, no statistically significant difference was found (P> 0.05). CONCLUSIONS: Compared with clopidogrel, ticagrelor appears to rapidly reduce the prevalence of inflammatory reactions and stabilize the functions of vascular endothelium to improve the stability of atherosclerotic plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome events without any obvious increase in the risk of bleeding in patients with acute STEMI receiving urgent PCI. This renders it a potential drug for clinical practice. At the same time, measurement of ESM-1, a new biological marker for vascular endothelial function disorder, could possibly become a simple, effective, and practical new method for clinical evaluation of risk stratification of patients with acute STEMI at admission.

Serum C1q/TNF-related protein 9 is not related to nonalcoholic fatty liver disease.

AIMS: C1q/TNF-related protein 9 (CTRP9) is an adipokine mainly secreted by white adipose tissue and plays protective roles in energy metabolism. However, information regarding the role of CTRP9 in nonalcoholic fatty liver disease (NAFLD) is scarce. Here we aimed to ascertain the clinical relevance between circulating CTRP9 levels and NAFLD through a cross-sectional study. METHODS: The study enrolled 82 NAFLD adults and 79 sex- and age-matched non-NAFLD controls. Serum CTRP9 was measured via ELISA method. Metabolic parameters were also determined. RESULTS: Although serum CTRP9 level seems to be higher in NAFLD adults, there was no significant difference among the ultrasonographic degrees of NAFLD (P = 0.275). Further, after adjustment for BMI in the multinomial logistic regression model, no significant odds ratio difference was observed for NAFLD among the CTRP9 tertiles. Moreover, binary logistic regression models demonstrated that, body mass index (BMI) and alanine aminotransferase (ALT) but not CTRP9 were independent factors related to NAFLD. Besides, serum CTRP9 was positively correlated with BMI, waist circumference, Fasting insulin, HbA1c, and HOMA-IR in all subjects. BMI was the independent factor associated with serum CTRP9. CONCLUSIONS: Serum CTRP9 is not independently related to NAFLD. The association between serum CTRP9 and NAFLD might be due to the influence of obesity.

Spontaneous conversion of atrial fibrillation caused by severe hyperkalemia: A case report.

RATIONALE: Hyperkalemia is a life-threatening electrolyte disturbance which could lead to arrhythmias and potentially death. PATIENT CONCERNS: An 82-year-old male patient who presented typical electrocardiographic indications of hyperkalemia, including the absence of P waves, prolongation of QRS complex, sinoventricular conduction, bradyarrhythmia and tall peaked T waves. He developed a rare self-defibrillation of atrial fibrillation to sinus rhythm due to hyperkalemia. Besides, he developed secondary thrombosis caused by abrupt termination of atrial fibrillation. DIAGNOSES: This patient was diagnosed with hyperkalemia, hypertension, and AF. INTERVENTIONS: He was treated with an intravenous infusion of calcium gluconate, insulin and dextrose, an oral kayexalate, and emergency hemodialysis. OUTCOMES: The patient was managed effectively and discharged with stable status. LESSONS: Hyperkalemia could induce malignant arrhythmia with high mortality. Thus we suggested more attention be paid to monitoring electrolyte disorders and maintaining anticoagulation treatments to avoid thromboembolism.

CFTR protects against vascular inflammation and atherogenesis in apolipoprotein E-deficient mice.

Atherosclerosis is a chronic inflammatory disease of the vascular wall. Dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to result in inflammatory responses in cystic fibrosis (CF) patients. However, little is known about the role of CFTR in vascular inflammation and atherogenesis. Our results showed that CFTR was dominantly expressed in macrophages of atherosclerotic plaque and reduced in aorta and aortic sinus from atherosclerotic apolipoprotein E-deficient (apoE-/-) mice. In vivo administration of adenovirus encoding CFTR (Ad-CFTR) with apoE-/- mice fed on high-fat diet (HFD) improved plaque stability by decreasing lipid accumulation and necrotic area and increasing smooth muscle cell content and collagen. The Ad-CFTR-treated mice also displayed reduced proinflammatory cytokines levels in aorta and peritoneal macrophages, whereas the anti-inflammatory M2 macrophage markers were increased. Confocal microscopy revealed that the infiltration of T lymphocytes, neutrophils, and macrophages in aortic sinus was markedly attenuated in Ad-CFTR-treated apoE-/- mice. Moreover, in vitro experiments showed that overexpression of CFTR inhibited ox-LDL-induced the migration of peritoneal macrophages. Finally, it was observed that CFTR up-regulation suppressed NFκB and MAPKs activity induced by ox-LDL. Inhibition of JNK or ERK abrogated CFTR down-regulation induced NFκB activation, whereas NFκB inhibitor had no effect on JNK or ERK activation. Taken together, these results demonstrate that CFTR prevents inflammation and atherogenesis via inhibition of NFκB and MAPKs activation. Our data suggest that CFTR may present a potential therapeutic target for the treatment of vascular inflammation and development of atherosclerotic disease.

Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice.

We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6-8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6-8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR. Phosphorylated and total TAK1, Akt, and p38 MAPK levels were examined by Western blotting. The ratios of lung or heart/body weight, wall thickness/chamber diameter of left ventricular and cross area of cardiomyocyte were significantly reduced in TRADD knockout (KO) mice than those of wild-type mice after TAC. Moreover, cardiac hypertrophic and fibrotic markers were downregulated in TRADD knockout mice than those of wild-type mice following TAC. Protein expression analysis showed phosphorylated TAK1, p38 MAPK and AKT were upregulated after TAC in both wild-type and TRADD KO mice, phosphorylation of TAK1 and p38 MAPK was reduced more remarkably after TRADD deficiency, while phosphorylated AKT expression was similar between TRADD KO and wild-type mice following TAC. Our data suggest that TRADD KO blunts pressure overload-induced cardiac hypertrophy through mediating TAK1/p38 MAPK but not AKT phosphorylation in mice.

Risk burdens of modifiable risk factors incorporating lipoprotein (a) and low serum albumin concentrations for first incident acute myocardial infarction.

Risk burdens of modifiable risk factors incorporating lipoprotein (a) (Lp(a)) and low serum albumin (LSA) concentrations for first incident acute myocardial infarction (AMI) haven't been studied previously. Cross-sectional study of 1552 cases and 6125 controls was performed for identifying the association of risk factors with first incident AMI and their corresponding population attributable risks (PARs). Modifiable risk factors incorporating LSA and Lp(a) accounted for up to 92% of PAR for first incident AMI. Effects of these risk factors were different in different sexes across different age categories. Overall, smoking and LSA were the 2 strongest risk factors, together accounting for 64% of PAR for first incident AMI. After multivariable adjustment, Lp(a) and LSA accounted for 19% and 41%, respectively, and together for more than a half (54%) of PAR for first incident AMI. Modifiable risk factors incorporating LSA and Lp(a) have accounted for an overwhelmingly large proportion of the risk of first incident AMI, indicating most first incident AMI is preventable. The knowledge of risk burdens for first incident AMI incorporating Lp (a) and LSA may be beneficial for further reducing first incident AMI from a new angle.

Ischemia triggered ATP release through Pannexin-1 channel by myocardial cells activates sympathetic fibers.

The cardiovascular system is extensively innervated by the autonomic nervous system, and the autonomic modulation including sympathetic innervation is crucial to the function of heart during normal and ischemic conditions. Severe myocardial ischemia could cause acute myocardial infarction, which is one of the leading diseases in the world. Thus studying the sympathetic modulation during ischemia could reduce the probability of myocardial infarction and further heart failure. The neurotransmitter ATP is released by myocardial cells during ischemia; however, the effect of ATP release remains elusive. We examined whether ATP released during ischemia functions as a neurotransmitter that activates sympathetic nerve in the heart. A novel technique of recording the sympathetic fiber calcium imaging in mouse cardiac tissue slices was used. We have applied the Cre/loxP system to specifically express GCaMP3, a genetically encoded calcium indicator, in the sympathetic nerve. Using this technique, we found that ATP released by myocardial cells through Pannexin-1 channel during ischemia could evoke calcium responses in cardiac sympathetic nerve fibers. Our study provides a new approach to study the cell and nerve interaction in the cardiac system, as well as a new understanding of ATP function during ischemia.

Olmesartan ameliorates pressure overload-induced cardiac remodeling through inhibition of TAK1/p38 signaling in mice.

AIMS: Many studies have demonstrated the potent effects of ARB administration on heart failure. However, the mechanism of the potent effects of ARB on cardiac remodeling is less well understood. We investigated the role of Olmesartan on the fibrosis and hypertrophy in mouse heart. MATERIALS AND METHODS: We employed TAC surgery, a mouse model of chronic cardiac failure. All the mice were separated into three groups: the sham group, TAC group and TAC plus Olmesartan group (given Olmesartan treatment after TAC). We analyzed left ventricle remodeling, and function by echocardiography or pathology. We further detected the level of marker genes involved in fibrosis and hypertrophy and in cultured neonatal rat cardiac fibroblasts and myocytes infected by constitutively active TAK1 and p38MAPK. After TAC, all the mice developed hypertrophy, worse cardiac function and malignant remodeling in left ventricle. KEY FINDINGS: Olmesartan improved heart remodeling and function without changing pressure of blood. Moreover, Olmesartan reduced the level of transforming growth factor ß activated kinase-1 (TAK1) and phospho-p38MAPK. In neonatal rat cardiac fibroblast cells and cardiomyocytes, Olmesartan also decreased TAK1 and p38MAPK activation triggered by TGFß1 or AngII. The inhibitory effect of Olmesartan was abrogated by overexpression of constitutively active TAK1 and p38MAPK by adenovirus system. SIGNIFICANCE: Our results suggest Olmesartan improves heart remodeling and function induced by pressure overload. P38MAPK inactivation attenuated by olmesartan via inhibition of TAK1 pathway plays an important role in the process.

Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways.

Intermedin is a proopiomelanocortin-derived peptide before opioid promoting cortical hormone, its main function embodies in mononuclear macrophages and neutrophilic granulocytes to inhibit the proinflammatory cytokines. The aim of this study is to determine intermedin attenuates myocardial infarction and its related mechanisms in a rat model of ischemic heart failure. After rat model of ischemic heart failure was set up, myocardial infarction, blood levels of activities of creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were effectively reduced by treatment with intermedin. Tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in a rat model of ischemic heart failure were recovered by pretreatment with intermedin. Administrate of intermedin availably promoted cAMP contents and suppressed caspase-3 protein in ischemic heart failure rat. ERK1/2 and LC3 protein expression were significantly activated and autophagy was significantly promoted by intermedin in a rat model of ischemic heart failure. These results indicate that intermedin protected rat heart, attenuates myocardial infarction from ischemic heart failure in the rat model. The underlying mechanisms may include upregulation of cAMP, ERK1/2 and LC3 protein expression and activating of autophagy.

A novel association of adenosine deaminase with paroxysmal atrial fibrillation: a propensity score analysis from a case-control study.

BACKGROUND: Prior work has identified age, body mass index, underlying heart disease, and other comorbidities as risk factors for atrial fibrillation. To date, studies have examined single baseline measures of traditional risk factors, and data on biomarker associations are lacking. OBJECTIVE: We sought to explore novel biochemical measures possibly associated with incident PAF after balancing the traditional risk factors. METHODS: Men or women aged ≥18 years that were hospitalized between 1(st) Jan. 2010 and 31(st) Dec. 2013 for paroxysmal atrial fibrillation (PAF) and for health checkup (non-PAF) were included. We used propensity score methods to mitigate the influence of the nonrandom selection of PAF and non-PAF patients. Logistic regression was applied for analysis of risk factors for PAF. RESULTS: A total of 1,802 eligible patients were identified, in whom, 895 patients had at least one exclusion criterion. After excluding these patients, the total analytic cohort numbered 907 patients. Of these, 779 patients were for control group and 128 patients were for PAF group. Propensity score matching was used to obtain a balanced cohort of 124 patients per group. The PAF and non-PAF groups were well matched on demographic and clinical characteristics after propensity matching. Risk factors for PAF on multivariate stepwise logistic regression model included adenosine deaminase (ADA) [odds ratio (OR) =0.9160, P=0.015, 95% confidence interval (CI): 0.8536-0.9829], mitral valvular regurgitation (OR =3.4611, P=0.001, 95% CI: 1.7000-7.0467) and left atrial diameter (OR =1.0913, P=0.001, 95% CI: 1.0387-1.1465). Only the ADA was a protective factor for the occurrence of PAF. CONCLUSIONS: The ADA seems to be associated with PAF. The current study provides new insights into the prevention and treatment of PAF.