Genome-wide investigation of lncRNAs revealed their tight association with gastric cancer.

BACKGROUND: Gastric cancer (GC) is a significant health issue globally, ranking as the fifth most common cancer with over 10,000 new cases reported annually. Long non-coding RNA (lncRNA) has emerged as a critical player in cellular functions, influencing GC's development, growth, metastasis, and prognosis. However, our understanding of lncRNA's role in the pathogenesis of GC remains limited. Therefore, it is particularly important to explore the relationship between lncRNA and gastric cancer. METHODS: we conducted a comprehensive analysis of RNA sequencing data from the GEO database and stomach adenocarcinoma (STAD) data from the TCGA database to identify lncRNAs that exhibit altered expression levels in GC and the mechanisms underlying lncRNA-mediated transcription and post-transcriptional regulation were explored. RESULTS: This study uncovered 94 lncRNAs with differential expression and, through co-expression analysis, linked these to 1508 differentially expressed genes (DEGs). GO functional enrichment analysis highlighted that these DEGs are involved in critical pathways, such as cell adhesion and the positive regulation of cell migration. By establishing a lncRNA-miRNA-mRNA regulatory network, we found that the ceRNA mechanism, particularly involving RP11-357H14.17 and CTD-2377D24.4, could play a role in GC progression. Experimental validation of selected differentially expressed lncRNAs and mRNAs (including RP11-357H14.17-CLDN1, BBOX1, TRPM2-AS, CLDN1, PLAU, HOXB7) confirmed the RNA-seq results. CONCLUSIONS: Overall, our findings highlight the critical role of the lncRNA-mRNA regulatory network in the development and progression of GC, offering potential biomarkers for diagnosis and targets for innovative treatment strategies.

Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

New Insights into Rate Control: Time in Target Range of Resting Heart Rate and Major Adverse Outcomes in Atrial Fibrillation.

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.

Safety of magnetic resonance imaging in patients with surgically implanted permanent epicardial leads.

BACKGROUND: Magnetic resonance imaging (MRI) safety in patients with an epicardial cardiac implantable electronic device (CIED) is uncertain. OBJECTIVE: The purpose of this study was to assess the safety and adverse effects of MRI in patients who had surgically implanted epicardial CIED. METHODS: Patients with surgically implanted CIEDs who underwent MRI with an appropriate cardiology-radiology collaborative protocol between January 2008 and January 2021 were prospectively studied in 2 clinical centers. All patients underwent close cardiac monitoring through MRI procedures. Outcomes were compared between the epicardial CIED group and the matched non-MRI-conditional transvenous CIED group. RESULTS: Twenty-nine consecutive patients with epicardial CIED (41.4% male; mean age 43 years) underwent 52 MRIs in 57 anatomic regions. Sixteen patients had a pacemaker, 9 had a cardiac defibrillator or cardiac resynchronization therapy-defibrillator, and 4 had no device generator. No significant adverse events occurred in the epicardial or transvenous CIED groups. Battery life, pacing, sensing thresholds, lead impedance, and cardiac biomarkers were not significantly changed, except 1 patient had a transient decrease in atrial lead sensing function. CONCLUSION: MRI of CIEDs with epicardially implanted leads does not represent a greater risk than transvenous CIEDs when performed with a multidisciplinary collaborative protocol centered on patient safety.

Investigation of the Temperature Compensation of Piezoelectric Weigh-In-Motion Sensors Using a Machine Learning Approach.

Piezoelectric ceramics have good electromechanical coupling characteristics and a high sensitivity to load. One typical engineering application of piezoelectric ceramic is its use as a signal source for Weigh-In-Motion (WIM) systems in road traffic monitoring. However, piezoelectric ceramics are also sensitive to temperature, which affects their measurement accuracy. In this study, a new piezoelectric ceramic WIM sensor was developed. The output signals of sensors under different loads and temperatures were obtained. The results were corrected using polynomial regression and a Genetic Algorithm Back Propagation (GA-BP) neural network algorithm, respectively. The results show that the GA-BP neural network algorithm had a better effect on sensor temperature compensation. Before and after GA-BP compensation, the maximum relative error decreased from about 30% to less than 4%. The sensitivity coefficient of the sensor reduced from 1.0192 × 10-2/°C to 1.896 × 10-4/°C. The results show that the GA-BP algorithm greatly reduced the influence of temperature on the piezoelectric ceramic sensor and improved its temperature stability and accuracy, which helped improve the efficiency of clean-energy harvesting and conversion.

Effect of different fertilizers on the physicochemical properties, chemical element and volatile composition of cucumbers.

The main purpose of the present study was to investigate the effect of different fertilizers on the physicochemical properties, multi-element and volatile composition of cucumbers. All samples were divided into five groups according to different combinations and amounts of chicken manure, NPK 17-17-17 fertilizer and microbial fertilizer. The co-application of chicken manure (120,000 kg/ha) and NPK 17-17-17 fertilizer (750 kg/ha) achieved the best texture properties, whereas the addition of the microbial fertilizer at 6000 kg/ha significantly improved the color quality of cucumbers. Similarly, the co-application of chicken manure, NPK 17-17-17 fertilizer and microbial fertilizer at 6000 kg/ha enhanced the number and abundance of volatile components detected in the cucumbers. Cucumbers from the control group contained the highest levels of most of the determined elements. Overall, a combination of chicken manure, NPK 17-17-17 fertilizer and 6000 kg/ha microbial fertilizer is recommended as a relatively efficient fertilizer utilization for cucumbers.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Electrophysiological characteristics of epicardial to endocardial breakthrough in intractable cavotricuspid isthmus-dependent atrial flutter.

BACKGROUND: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL. METHODS: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed. RESULTS: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence. CONCLUSIONS: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally.

Spectral characterization and impact of stepwise ablation protocol including LAA electrical isolation on persistent AF.

OBJECTIVES: To study how left atrial appendage electrical isolation (LAAEI) impacts atrial dominant frequency (DF) in patients with long-standing persistent atrial fibrillation (LSPAF). BACKGROUND: LAAEI is associated with a high probability of freedom from atrial fibrillation (AF) and spectral analysis may identify high-frequency sources. How LAAEI impacts the AF dynamics and the subgroup of LSPAF patients in whom LAAEI would be most beneficial, is unclear. METHODS: Twenty patients with LSPAF were included in the study. Fast Fourier transforms (FFT) were performed on atrial electrograms recorded from 13 sites in the LA and RA. The highest peak frequency was defined as DF. RESULTS: There was no significant difference in DF between atrial sites except for at the superior vena cava which had the lowest DF at baseline. Stepwise ablation consisting of circumferential pulmonary vein isolation and a linear ablation set of mitral isthmus and roof significantly reduced the DF within the coronary sinus (CS) (5.93 ± 0.98 Hz vs. 5.09 ± 0.72 Hz, p < .05) and the LA posterior wall (LApos) (6.26 ± 0.92 Hz vs. 5.43 ± 0.98 Hz, p < .01). LAAEI preferentially further decreased the DF at the LApos (p < .01), but not at the CS. In cases where there was < 13.6% reduction in the DF of the LApos following the stepwise ablation, the addition of LAAEI was associated with an increased restoration of sinus rhythm (55%, p < .05). CONCLUSION: LAAEI in addition to stepwise ablation results in further reduction of the DF in the LApos, which is associated with acute termination of AF and favorable ablation outcome.

Automatic annotation of local activation time was improved in idiopathic right ventricular outflow tract ventricular arrhythmia by novel electrogram "Lumipoint" algorithm.

PURPOSE: Precise automatic annotation of local activation time (LAT) is crucial for rapid high-density activation mapping in arrhythmia. However, it is still challenging in voltage-transitional areas where local low-amplitude near-field potentials are often obscured by large far-field potentials. The aim of this study was to explore the viability and validity of automatic identification of the earliest activation (EA) in idiopathic right ventricular outflow tract ventricular arrhythmias (RVOT VAs) using a novel Lumipoint algorithm. METHODS AND RESULTS: Twenty-seven patients with RVOT VAs were mapped with Rhythmia mapping system. Lumipoint algorithms were applied to reannotate the initial activation regions retrospectively. The results showed that LATs were reannotated in 35.0 ± 11.4% points in the initial activation area from bipolar activation breakout time (BBO) to the its 40 ms earlier timepoint. The automatically determined bipolar earliest activation time after Lumipoint reannotation (BEAT-lu: - 111.26 ± 12.13 ms) was significantly earlier than that before (BEAT: - 108.67 ± 12.25 ms, P = 0.000). Compared with manually corrected earliest activation time (EAT), the difference between EAT and BEAT-lu (DEAT-BEAT-lu: 6 (2-7) ms) was significantly smaller than that between EAT and BEAT (DEAT-BEAT/DEAT-UEA: 7 (4-11) ms, P = 0.000). The incidence of EAT and BEAT-lu being the same site was significantly higher than that between EAT and BEAT (48.15% vs 18.52%, P = 0.021). CONCLUSIONS: RVOT VAs often originate from voltage-transitional zone, and automatic annotation of LAT usually located at later high-amplitude far-field potential. Lumipoint algorithms could improve the accuracy of LAT automatic annotation, and it was plausible to ablate RVOT VAs just according to the automatically annotated BEAS-lu.

A novel HDGF-ALCAM axis promotes the metastasis of Ewing sarcoma via regulating the GTPases signaling pathway.

Ewing sarcoma (ES) is a type of highly aggressive pediatric tumor in bones and soft tissues and its metastatic spread remains the most powerful predictor of poor outcome. We previously identified that the transcription factor hepatoma-derived growth factor (HDGF) promotes ES tumorigenesis. However, the mechanisms underlying ES metastasis remain unclear. Here, we show that HDGF drives ES metastasis in vitro and in vivo, and HDGF reduces metastasis-free survival (MFS) in two independent large cohorts of human ES patients. Integrative analyses of HDGF ChIP-seq and gene expression profiling in ES cells reveal that HDGF regulates multiple metastasis-associated genes, among which activated leukocyte cell adhesion molecule (ALCAM) emerges as a major HDGF target and a novel metastasis-suppressor in ES. HDGF down-regulates ALCAM, induces expression and activation of the downstream effectors Rho-GTPase Rac1 and Cdc42, and promotes actin cytoskeleton remodeling and cell-matrix adhesion. In addition, repression of ALCAM and activation of Rac1 and Cdc42 are required for the pro-metastatic functions of HDGF in vitro. Moreover, analyses in murine models with ES tumor orthotopic implantation and experimental metastasis, as well as in human ES samples, demonstrate the associations among HDGF, ALCAM, and GTPases expression levels. Furthermore, high HDGF/low ALCAM expression define a subgroup of patients harboring the worst MFS. These findings suggest that the HDGF/ALCAM/GTPases axis represents a promising therapeutic target for limiting ES metastasis.

Overdrive pacing mapping: An alternative approach used in scar associated localized atrial tachycardia.

BACKGROUND: Mapping and ablation of localized reentry atrial tachycardia (AT) can be challenging, especially in those with varying cycle length (CL). OBJECTIVE: We attempted to use the traditional maneuver of overdrive pacing to facilitate AT mapping. METHODS: Data were collected from 12 patients with localized ATs. All patients had prior cardiac surgery or prior atrial fibrillation ablation. Overdrive pacing mapping (ODPM) was performed to find independent local activity (ILA) and compared with conventional activation mapping (CAM) during ongoing AT to determine its accuracy and efficacy. Patients with macro-reentry AT around the tricuspid or mitral annulus were excluded. RESULTS: Twelve patients with 14 localized ATs were included. All 14 ATs including 4 (29%) with varying CL successfully completed ODPM and had the ILA, although two ATs terminated during ODP and required repeated mapping. Radiofrequency ablation focused on critical sites with ILA was successful in all 12 patients. Using CAM, however, 6 of 14 ATs (43%) mapping attempts were aborted due to AT termination (2 ATs) or varying CL (4 ATs), and only 5 of 8 (63%) located "critical sites" were ultimately confirmed by entrainment and ablation results. After 25 ± 9 months of follow-up, no patient had AT recurrence. CONCLUSION: Our preliminary results demonstrated that ODPM is superior to CAM in ATs that were poorly sustained or with varying CL and is a useful supplement to CAM.

Tachycardia cycle length alternans caused by alternate conduction velocity on the slow conduction zone in a postoperative scar-related atrial tachycardia.

The underlying mechanism for stable beat-to-beat cycle length variability (CL alternans) in scar-related atrial tachycardia (AT) had not been elucidated clearly. We described a case with postoperative dual-loop reentrant AT in right atrium. When the loop depended on cavo-tricuspid isthmus was blocked by ablation, the AT transformed into a CL alternate tachycardia. High density and resolution mapping revealed that the CL alternans was caused by the alternate conduction velocities at the slow conduct region. A further ablation line was created from the slow conduction zone to the inferior vena cave, and afterward no AT was inducible.

Electrophysiological characteristics of the earliest activation site in idiopathic right ventricular outflow tract arrhythmias under mini-electrode mapping.

INTRODUCTION: Right ventricular outflow tract ventricular arrhythmias (RVOT VAs) often originate in the voltage-transitional zone. The target electrogram could be compromised by the architecture of the roving catheter. Mini-electrodes could improve the mapping resolution, especially in low-voltage areas. The aim was to assess the electrophysiological characteristics of the earliest activation site (EAS) of RVOT VAs during mapping using mini-electrodes. METHODS AND RESULTS: Twenty-seven patients with RVOT-type VAs were mapped using Orion mini-electrodes and the Rhythmia mapping system. Bipolar and unipolar electrograms were analyzed and compared with conventional ablation catheter recordings. Twenty-five patients (25 of 27) were successfully mapped and ablated at the RVOT. At the EAS, all 25 (100%) patients exhibited local sharp potentials (spiky potential) at the VAs, and 88% (22 of 25) individuals showed reverse late potentials in adjacent sinus beats on the bipolar mini-electrode recordings. Related unipolar electrograms manifested 20% "q-plateau-QS," 76% "gross QS," and 4% "late QS" patterns related to spiky potential voltages and advanced times. Compared with electrograms recorded by ablation catheter, bipolar mini-electrode recordings exhibited significantly shorter spiky potential durations (P = 0.001) and a significantly increased incidence of the reverse late potentials (P = 0.041). Unipolar mini-electrode recordings had a lower incidence ratio of "late QS" patterns (P = 0.039). CONCLUSION: Compared with ablation catheter mapping, mini-electrodes improved the mapping resolution of the EAS of RVOT VAs and exhibited shorter spiky potential durations and reduced incidence of "later QS" unipolar patterns.

Experimental and simulation research on the screening effect of the pixelated CZT imaging detector.

Massive efforts have been made to investigate the characteristics of the CdZnTe detector under different extreme conditions. In this paper, we experimented with different radiation sources to investigate the imaging screening effect of the pixelated CdZnTe detector under ultrahigh irradiance. A donut-shaped irradiation image was obtained due to the increase in the X-ray tube current or the tube voltage. Moreover, statistical data revealed that the total count of all pixels was not significantly different, while the event-count of irradiated area pixels decreased significantly. A consequence of the screening effect was that the event counts redistributed among pixels that are located in the irradiated area, while the inner electric field was distorted. This leads to the catastrophic performance degradation of the central pixels. According to the Poisson equation, we developed a theoretical model of the CdZnTe detector using the finite element software COMSOL to enable an in-depth investigation of carrier collection in the CdZnTe crystal. A comparison between the simulations and the test results showed that pixels in the central irradiated area are completely screened under the ultrahigh irradiance because of the emergence of the relatively higher potential region, which can distort the electron drift path. Furthermore, the photon-generated signal can be collected only partly at the edge of the irradiated area, which was relatively stable because the collection area in the CdZnTe volume was relatively limited. The imaging results deduced from the simulations are well consistent with the experimental data.

Association between paced QRS duration and atrial fibrillation after permanent pacemaker implantation: A retrospective observational cohort study.

Right ventricular pacing often results in prolonged QRS duration (QRSd) as the result of right ventricular stimulation, and atrial fibrillation (AF) may result. The association of pacing-induced prolonged QRSd and AF in patients with permanent pacemakers is unknown.We selected 180 consecutive patients who underwent pacemaker implantation for complete/advanced atrioventricular block. All of the patients were paced from the right ventricular septum. Electrocardiography recordings were obtained at the beginning and the end of pacemaker implantation. QRSd was measured in all 12 leads. The QRSd variation was calculated by subtracting the preimplantation QRSd from the postimplantation QRSd.The occurrence of AF was observed in 64 (35.56%) patients (follow-up 33.62 ±â€Š21.47 mo). No significant differences in preimplantation QRSd were observed between the AF occurrence and nonoccurrence groups. The QRSd variation in leads V4 (54.22 ±â€Š29.03 vs 42.66 ±â€Š33.79 ms, P = .022), and V6 (64.62 ±â€Š23.16 vs 48.45 ±â€Š34.40 ms, P = .001) differed significantly between the occurrence and nonoccurrence groups. More QRSd variation in lead V6 (P = .005, HR = 1.822, 95% CI 1.174-2.718, interval scale of QRSd was 40 ms) and left atrial diameter (P = .045, HR = 1.042, 95% CI 1.001-1.086) were independent risk factors for AF occurrence. Receiver operating characteristic curve suggested that QRSd variation in lead V6 could predict AF occurrence, especially for patients with long preimplantation QRSd (≥120 ms, area under the curve was 0.826, 95% CI 0.685-0.967).QRSd variation in lead V6 might be positively correlated with postimplantation AF occurrence. In patients with pacemaker implantation, QRSd could be a complementary criterion for optimizing the right ventricular septal pacing site, and smallest QRSd might be worth pursuing.

An unusual 'rite of passage' for an ablation catheter during left ventricular tachycardia ablation - a case report.

INTRODUCTION: Ventricular perforation during radiofrequency ablation of ventricular tachycardia is a recognized serious complication that carries high morbidity and mortality. Perforation is often associated with local intramyocardial injury due to excess heat induced by catheter, 'steam pop'. The complication usually requires emergency surgical repair. CASE PRESENTATION: We present a case, when the catheter found its way into the epicardium during left ventricular (LV) electroanatomic mapping without any serious complication. Angiography through the ablation catheter confirmed the diagnosis of LV coronary sinus fistula. DISCUSSION: Contrast injection through the irrigation port of the ablation catheter is a useful way of delineating anatomical anomalies during electrophysiology procedure.

AMPK attenuates ventricular remodeling and dysfunction following aortic banding in mice via the Sirt3/Oxidative stress pathway.

Although recent findings have suggested that AMP-activated protein kinase (AMPK) exerts inhibitory effects on cardiac remodeling secondary to hypertension, the mechanism and optimal duration of treatment remain unknown. Mice with descending aortic banding (AB) or subjected to sham operation received subcutaneous injection of either AICAR (0.5mgg-1day-1) or vehicle over 4 week periods. At the end of 4 week treatment, left ventricular (LV) remodeling and function were evaluated with histological analysis and echocardiography. Collagen deposition within the LV myocardium was detected with Masson's trichrome staining. Collagen I, Collagen III, Smad 2, Smad 3, NOX2, NOX4 and Sirt3 (an important antioxidant factor) within the LV tissue were also evaluated. Compared with the sham group, the vehicle-treated AB group exhibited significant elevations in cardiac remodeling and heart failure, characterized by an increase in LV weight relative to body weight, an increase in the area of collagen deposition, an increase in LV end-diastolic diameter, an increase in mitral E inflow velocity to mitral A inflow velocity and increases in the gene expressions of the fibrosis markers Collagen I, III and Smad 2, 3 mRNA and decreases in EF and fractional shortening. AMPK attenuate the cardiac remodeling parameters and improve cardiac function. Moreover, the expressions of NOX2, NOX4 were significantly elevated in vehicle-treated AB group. AMPK was able to significantly inhibit NOX2, NOX4 expression, while activate Sirt3 expression. AMPK significantly attenuated hypertension-induced Ventricular remodeling and dysfunction, which may be mediated by the Sirt3/Oxidative stress signaling pathway.

A meta-analysis of low-dose dopamine in heart failure.

BACKGROUND: Heart failure (HF) is a major health problem worldwide with no proven therapy. Low-dose dopamine (LDD) has been applied to patients with HF to enhance diuresis and preserve renal function since the last century. However, the efficacy of LDD in HF has been questioned by several studies recently. The purpose of this meta-analysis is to appraise the effects of the LDD to HF. METHODS: Relative trials were identified in the PubMed, The Web of Science, OVID EBM Reviews and Cochrane databases, and the relevant papers were examined. Pooled mean difference (MD) and 95% confidence interval (95% CI) were estimated by random effects models. The primary endpoints in our meta-analysis were renal function, determined by blood urea, creatinine levels, eGFR and urine output. Secondary endpoints were rates of all-cause mortality and readmission after treatment. RESULTS: Six randomized controlled trials (RCTs) and one retrospective study involving 587 patients were included in this analysis. LDD enhanced eGFR (MD, 7.44; 95% CI, 1.92-12.95; P=0.008), urine output (SMD, 0.58; 95% CI, 0.15-1.01; P=0.008) and decrease creatinine levels (MD, -0.36; 95% CI, -0.64/-0.08; P=0.004), blood urea (MD, -6.97; 95% CI, -13.12/-0.81; P=0.03). No statistically significant differences in the rates of mortality (RR, 0.86; 95% CI, 0.62-1.20, P=0.37) and readmission (RR: 0.86; 95% CI 0.47-1.56, P=0.62) were noted. CONCLUSIONS: LDD indeed brought benefits in terms of promoting diuresis and preserving renal function for HF patients. It did not demonstrate statistical significance in rates of readmission nor mortality. The efficacy of LDD to HF patients should be confirmed by further large, high quality clinical trials.

Adenosine monophosphate-activated protein kinase attenuates cardiomyocyte hypertrophy through regulation of FOXO3a/MAFbx signaling pathway.

Control of cardiac muscle mass is thought to be determined by a dynamic balance of protein synthesis and degradation. Recent studies have demonstrated that atrophy-related forkhead box O 3a (FOXO3a)/muscle atrophy F-box (MAFbx) signaling pathway plays a central role in the modulation of proteolysis and exert inhibitory effect on cardiomyocyte hypertrophy. In this study, we tested the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation attenuates cardiomyocyte hypertrophy by regulating FOXO3a/MAFbx signaling pathway and its downstream protein degradation. The results showed that activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) attenuated cardiomyocyte hypertrophy induced by angiotensin II (Ang II). The antihypertrophic effects of AICAR were blunted by AMPK inhibitor Compound C. In addition, AMPK dramatically increased the activity of transcription factor FOXO3a, up-regulated the expression of its downstream ubiquitin ligase MAFbx, and enhanced cardiomyocyte proteolysis. Meanwhile, the effects of AMPK on protein degradation and cardiomyocyte hypertrophy were blocked after MAFbx was silenced by transfection of cardiomyocytes with MAFbx-siRNA. These results indicate that AMPK plays an important role in the inhibition of cardiomyocyte hypertrophy by activating protein degradation via FOXO3a/MAFbx signaling pathway.