Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo.

Introduction: Sepsis is a life-threatening disease that damages multiple organs and induced by the host's dysregulated response to infection with high morbidity and mortality. Heart remains one of the most vulnerable targets of sepsis-induced organ damage, and sepsis-induced cardiomyopathy (SIC) is an important factor that exacerbates the death of patients. However, the underlying genetic mechanism of SIC disease needs further research. Methods: The transcriptomic dataset, GSE171564, was downloaded from NCBI for further analysis. Gene expression matrices for the sample group were obtained by quartile standardization and log2 logarithm conversion prior to analysis. The time series, protein-protein interaction (PPI) network, and functional enrichment analysis via Gene Ontology and KEGG Pathway Databases were used to identify key gene clusters and their potential interactions. Predicted miRNA-mRNA relationships from multiple databases facilitated the construction of a TF-miRNA-mRNA regulatory network. In vivo experiments, along with qPCR and western blot assays, provided experimental validation. Results: The transcriptome data analysis between SIC and healthy samples revealed 221 down-regulated, and 342 up-regulated expressed genes across two distinct clusters. Among these, Tpt1, Mmp9 and Fth1 were of particular significance. Functional analysis revealed their role in several biological processes and pathways, subsequently, in vivo experiments confirmed their overexpression in SIC samples. Notably, we found TPT1 play a pivotal role in the progression of SIC, and silencing TPT1 showed a protective effect against LPS-induced SIC. Conclusion: In our study, we demonstrated that Tpt1, Mmp9 and Fth1 have great potential to be biomarker of SIC. These findings will facilitated to understand the occurrence and development mechanism of SIC.

PEG-modified carbon-based nanoparticles as tumor-targeted drug delivery system reducing doxorubicin-induced cardiotoxicity.

Herein, a doxorubicin-loaded carbon-based drug delivery system, denoted as PC-DOX, composed of pH-responsive imine bond was developed for the tumor-targeted treatment. PC-DOX with a uniform particle size around 180 nm was synthesized by coating of as-synthesized hollow carbon-based nanoparticles (NPs) with dialdehyde PEG, which was used as carrier to attach DOX covalently through dynamic covalent bond. The unique structure endowed the advantages of specific tumor targeting and tumor microenvironment (TME) specific drug delivery capacity with PC-DOX. For the one hand, the tumor targeting caused by the enhanced permeability and retention (EPR) effect could significantly improve the tumor cellular uptake. For the other hand, the pH-responsiveness could realize the effective DOX accumulation in tumor tissues, avoiding the unwanted side effect to the normal tissues. As a result, PC-DOX with high DOX loading capacity (70.12%) and excellent biocompatibility, concurrently, presented a significant anti-tumor effect at a low mass concentration (DOX equivalent dose: 20 µg/mL). Another attractive characteristic of PC-DOX was the remarkable protective effect towards DOX-induced cardiotoxicity, which could be clearly observed from in vitro cellular, and animal assays. Compared with free DOX, the cardiomyocyte viability increased by average 30.58%, and the heart function was also significantly improved. This novel drug delivery nanoplatform provides a new method for the future clinical application of DOX in the cancer's therapeutics.

Biodegradable porous polymeric drug as a drug delivery system: alleviation of doxorubicin-induced cardiotoxicity via passive targeted release.

Doxorubicin (DOX) is an effective chemotherapeutic drug developed against a broad range of cancers, and its clinical applications are greatly restricted by the side effects of severe cardiotoxicity during tumour treatment. Herein, the DOX-loaded biodegradable porous polymeric drug, namely, Fc-Ma-DOX, which was stable in the circulation, but easy to compose in the acidic medium, was used as the drug delivery system avoiding the indiscriminate release of DOX. Fc-Ma was constructed via the copolymerization of 1,1'-ferrocenecarbaldehyde with d-mannitol (Ma) through the pH-sensitive acetal bonds. Echocardiography, biochemical parameters, pathological examination, and western blot results showed that DOX treatment caused increased myocardial injury and oxidative stress damage. In contrast, treatment with Fc-Ma-DOX significantly reduced myocardial injury and oxidative stress by DOX treatment. Notably, in the Fc-Ma-DOX treatment group, we observed a significant decrease in the uptake of DOX by H9C2 cells and a significant decrease in reactive oxygen species (ROS) production.

[Accumulation and Transport Characteristics of Cd, Pb, Zn, and As in Different Maize Varieties].

The enrichment and translocation characteristics of Cd, Pb, Zn, and As by various parts of maize plants were investigated using field experiments in 22 maize varieties simultaneously under uncontaminated, low, middle, and serious heavy metal Cd, Pb, Zn, and As complex-contaminated farmland soil conditions. The relationship between the uptake of Cd, Pb, Zn, and As by maize plants and the morphological content of heavy metals in the soil was also discussed through principal component analysis and correlation analysis of the concentrations of eight heavy metals, including Cd, Hg, As, Pb, Cr, Cu, Ni, and Zn. The results showed that:① the distribution pattern of Cd and Zn contents in different parts of the maize plant was as follows:upper stalk>lower stalk>root>seed, the distribution pattern of Pb was As follows:root>lower stalk>upper stalk>seed, and the As distribution pattern was:root>upper stalk>lower stalk>seed. The different distribution patterns were closely related to the accumulation characteristics of the crop itself and the environmental activity of Cd, Pb, Zn, and As in the soil of the study area. ② There were significant differences in Cd and Pb accumulation among 22 maize cultivars due to their genetic background (P<0.05), which showed four trends:Cd and Pb compound high-accumulation varieties, single Cd or Pb low-accumulation varieties (low Cd and high Pb, low Pb and high Cd), and Cd and Pb compound low-accumulation varieties. Among them, the content of Cd in the grain of the three varieties exceeded the national food safety standard, and the content of Cd in the stem and leaf of 14 varieties exceeded the national food health standard. The Pb content in stems, leaves, and grains of all cultivars did not exceed the standard, but the Pb content in grains of some cultivars was close to the limit and had the risk of exceeding the standard. The content of As in the stem, leaf, and grain of different maize varieties was much lower than the standard limit value, showing a stable low-accumulation characteristic. The content of Zn in the stem and leaf of different maize varieties increased with the increase in the content of Zn in soil, but the content of Zn in grain remained within the threshold of normal plant growth. ③ Cd, Pb, Zn, and As in maize plants in the study area had a certain homology and were mainly affected by the excessive levels of Cd, Pb, Zn, and As pollutants in the soil. This showed that anthropogenic sources were brought about by mine extraction and tailings stockpiles, whereas Cu elements in maize plants were affected by certain anthropogenic pollution sources, though to a limited extent. Hg, Ni, and Cr in maize plants had a certain homology; this showed the natural source of soil parent material and weathering product accumulation. ④ The contents of Cd, Pb, Zn, and As elements in various parts of the corn plant, as well as the contents of Cr and Ni elements all had a very significant positive correlation (P<0.01). The transport mechanisms of Cd, Pb, Zn, and As elements in the plant may have a common. However, there was a synergistic effect in the migration from the root of the corn to the upper part of the ground, and the same was true for the elements of Cr and Ni. The elements of Hg and Cd, Pb, Zn, and As in the corn stems and leaves and Hg and Cd, Hg, As, Pb, Cr, Ni, and Zn in grains all showed certain antagonistic effects. ⑤ The comparison method simultaneously satisfied the following requirements:the contents of Cd, Pb, and As in stems and leaves did not exceed the national food hygiene standards, and the contents of Cd, Pb, and As in the grains did not exceed the national food safety standards. The cluster analysis of Cd, Pb, and As in grains was a low-accumulation group, and the enrichment and transport coefficients of Cd, Pb, and As in the stems and leaves and grains were low as the optimal conditions. C18 (Xianyu 335) could be selected as the optimal maize variety with low accumulation of Cd, Pb, and As and normal Zn content in grain, which is suitable for promoting and applying in the heavy metal complex-polluted farmland around industrial and mining enterprises in north China.

Utilizing Network Pharmacology and Molecular Docking Integrated Surface Plasmon Resonance Technology to Investigate the Potential Targets and Mechanisms of Tripterygium wilfordii against Pulmonary Artery Hypertension.

Background: Pulmonary artery hypertension (PAH) is a rare, life-limiting cardiopulmonary disorder characterized by the progressive and remodeling of pulmonary vasculature. Although the development of the technology brings us many approaches for the treatment of PAH, the effect of treatment is unsatisfactory. Tripterygium wilfordii (TW), as a traditional Chinese medicine (TCM), has been widely used in anti-inflammation, anticancer, and other fields. However, the potential of TW in treating PAH is currently unclear. Methods: Active ingredients and their corresponding genes were harvested from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), CTD, and STITCH. Meanwhile, genes associated with PAH were adopted from OMIM and GeneCards databases. Through Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses, potential targeting KEGG pathways and functions were further collected. Then, STRING was used to generate the protein-protein interaction (PPI) network. The "ingredients-targets-pathway" network was built by Cystoscope. Finally, the binding between active ingredients of TW and corresponding targets of PAH was identified via molecular docking technology and surface plasmon resonance (SPR) experiments. Results: The network pharmacology analysis revealed 36 active ingredients in TW and 150 potential targets related to the treatment of PAH with TW. Moreover, GO enrichment analysis showed that the key function in molecular function (MF) was related to enzyme binding, the key function in biological process (BP) was related to cellular response to organic substance, and the key function in cellular component (CC) was related to KEGG enrichment analysis and found that it was closely related to the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and apoptosis. At last, molecular docking results revealed that the main active ingredients of TW had a strong binding ability with the PAH target protein. In addition, the SPR experiment revealed that kaempferol was combined with the CASP3 protein rather than PARP1, while triptolide was combined with PARP1 rather than the CASP3 protein. Conclusion: TW may have therapeutic effects on PAH through multitargets and multimethods, which provide a scientific basis for further elaborating the mechanism of Tripterygium wilfordii in the treatment of PAH.

[Synergistic Repair Effect of Calcite-Based Passivator and Low-Accumulation Maize].

In this study, a field experiment of soil passivation and low accumulation-crops was carried out for typical northern alkaline cadmium and lead compound-polluted farmland soil. Calcite was used as the main passivation material, and a small amount of slaked lime, zeolite powder, and biochar were combined to form a group passivation agent. The effects of passivators on soil physicochemical properties, bioavailability of the heavy metals Cd and Pb, and the yield and plant (stalk and seed) content of heavy metals Cd and Pb in low-accumulation maize were investigated under different grouping conditions of calcite+slaked lime (CL), calcite+zeolite (CZ), calcite+biochar (CB), and calcite+slaked lime+zeolite+biochar (CLZB). The results showed that:① all applications of passivating agent ensured the normal growth of maize and slightly increased the 1000 grain weight and maize yield. ② The effects of different calcite-based passivators on soil physical and chemical properties were different. The CL, CZ, CB, and CLZB treatments increased soil pH by 0.46, 0.25, 0.12, and 0.13 units, respectively, but had no significant correlation with soil fertility index (P>0.05). ③ DTPA leaching and ion exchange state contents of Cd and Pb in soil could be significantly reduced by different calcite-based combinations with passivators, and the reduction rates of Cd and Pb in DTPA leaching were 49.36% and 72.55%, respectively. The reduction rates of ion exchange Cd and Pb contents were 55.39% and 78.52%, respectively. ④ The contents of Cd and Pb in stems, leaves, and grains of low-accumulation maize were further reduced by different passivating agents. The contents of Cd and Pb in the stems and leaves of maize were reduced by 45.93% and 67.00% after CLZB treatment, and the contents of Cd and Pb in grains were decreased by 25.17% and 46.62%, respectively. Moreover, the contents of Cd and Pb in DTPA extraction and ion exchange states were significantly positively correlated with the contents of Cd and Pb in corn stems, leaves, and grains (P<0.01). The results showed that the combined use of combination passivators and low-accumulation crop varieties can obtain better restoration effects in the remediation of cadmium and lead combined-polluted farmland in the middle alkaline soil in northern China.

[Cadmium Accumulation Characteristics of Different Heat Varieties Under Cadmium Stress].

In order to provide technical support for the safe utilization of heavy metal-polluted farmland, we screened wheat varieties with a low accumulation of Cd in grain via a pot experiment. For this purpose, we respectively investigated the enrichment and transport characteristics of Cd in various plant parts of 119 wheat varieties under the conditions of 1.5 mg·kg-1 (low content) and 4.0 mg·kg-1 (high content) Cd-contaminated soil and explored the correlation between the Cd content of different organs of wheat and the relationship between Cd content in soil and the uptake of Cd by wheat. The results showed that:① there were significant differences in the ability to accumulate and transport Cd in roots, stems, leaves, and grains of tested wheat varieties (P<0.05). Under the condition of low Cd content, the Cd enrichment ability of each part of the wheat plant was as follows:leaf>stem ≈root>grain; under high-content stress conditions, the Cd enrichment ability of each part of the wheat plant was:leaf>root>stem>grain; under different content conditions, the Cd transport ability of each part of the wheat plant was:leaf>stem>grain. Cd content in the wheat shoot was positively correlated with total Cd content and ion-exchangeable Cd content in soil (P<0.01) and was closely related to strong transpiration under the pot experiment. ② The correlation coefficient r of BCFCd of wheat roots, stems, leaves, and grain was -0.267 to -0.645, showing a very significant negative correlation (P<0.01), indicating that with the increase in soil Cd content, the migration and accumulation degree of Cd in wheat plant organs showed a downward trend. Moreover, the negative correlation between BCFCd and soil Cd content in stems was significantly higher than that in roots, leaves, and grains, indicating that the enrichment of Cd in wheat plants largely depended on the accumulation and transportation of stems. ③ The correlation coefficient r of Cd content between the root and stem, root and leaf, root and grain, stem and leaf, stem and grain, and leaf and grain in low-and high-content groups was 0.450-0.763, showing a very significant positive correlation (P<0.01), indicating that there was a close transport relationship among the wheat organs, and the degree of translocation from the root to stem and stem to leaf was higher than that from the stem to grain and leaf to grain. ④ Using cluster analysis and enrichment and translocation coefficient sequencing, this study screened 16 and 11 wheat varieties with low Cd accumulation under the soil cadmium content of 1.5 mg·kg-1and 4.0 mg·kg-1, respectively. Among them, Luohan 7 could be used as the optimal wheat variety with low Cd accumulation under the conditions of low-, medium-, and high-Cd content.

Identification of tRNA-derived Fragments and Their Potential Roles in Atherosclerosis.

OBJECTIVE: Atherosclerosis (AS), a chronic inflammatory disease, is the basis of cardiovascular disease (CVD). Although the treatment has been greatly improved, AS still imposes a large burden on human health and the medical system, and we still need to further study its pathogenesis. As a novel biomolecule, transfer RNA-derived fragments (tRFs) play a key role in the progression of various disease. However, whether tRFs contribute to atherosclerosis pathogenesis remains unexplored. METHODS: With deep sequencing technology, the change of tRFs expression profiles in patients with AS compared to healthy control group was identified. The accuracy of the sequencing data was validated using RT qPCR. Subsequently, we predicted the potential target genes of tRFs by online miRNA target prediction algorithms. The potential functions of tRFs were evaluated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS: There were 13 tRFs differentially expressed between patients with AS and healthy controls, of which 2 were up-regulated and 11 were down-regulated. Validation by RT-qPCR analysis confirmed the sequencing results, and tRF-Gly-GCC-009 was highly up-regulated in the AS group based on the results of sequencing which was confirmed by RT-qPCR analysis. Furthermore, GO enrichment and KEGG pathway analyses indicated that 10 signaling pathways were related to tRF-Gly-GCC-009. These pathways might be physiopathological fundamentals of AS, mainly involving in Apelin signaling, Notch signaling and calcium signaling. CONCLUSION: The results of our study provide important novel insight into the underlying pathogenesis and demonstrate that tRFs might be potential biomarkers and therapeutic targets for AS in the future.

Effect and mechanisms of synthesis conditions on the cadmium adsorption capacity of modified fly ash.

In this study, modified coal fly ash (NMFA) was prepared by sodium hydroxide (NaOH) with low-temperature hydrothermal method. The differences of the ash to alkali mass ratio (5:3, 5:4, 5:5, 5:6), calcination temperature (100 â„ƒ, 200 â„ƒ, 300 â„ƒ), and calcination time (1 h, 3 h, 5 h) were investigated. The adsorption experiments obtained the optimal result with the ash to base ratio of 5:5, calcination temperature of 200 â„ƒ, and calcination time of 3 h, adsorbing 90.27 mg/g of Cd2+. The characterization results (SEM-EDS, FTIR, XRD, and XPS) also confirmed the effective adsorption of Cd2+ by NMFA. The functional groups of Si-O, Al-O, and Fe-O played an important role in Cd2+ removal. Meanwhile, the influences of dosage, different pH, and co-existing cations were also investigated. Quasi-secondary adsorption kinetics and Langmuir isotherm model were also referred to the Cd2+ adsorption by NMFA. Therefore, the good adsorption of NMFA-3 on Cd2+ provided new ideas for the safe utilization of fly ash and heavy metal purification in wastewater.

Potential of a novel modified gangue amendment to reduce cadmium uptake in lettuce (Lactuca sativa L.).

In this study, the modified gangue (GE) was prepared by calcination at lower temperatures using potassium hydroxide (KOH) as the activating agent. The field emission scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), and X-ray fluorescence (XRF) methods were employed to analyze the physicochemical characteristics of GE before and after the modification. Besides, the GE and commercial zeolite (ZE) were compared in the remediation of Cd-contaminated soil in field experiments. The results showed that both the GE and ZE had positive effects on the stabilization of Cd, decreasing the available Cd by 21.2-33.9% and 22.1-28.2%, respectively, while no significant difference was observed between the two amendments, indicating that the modification of GE was successful. Moreover, the application of GE decreased the Cd mobilization and uptake in lettuce shoot and root by 54.9-61.5% and 9.3-13.2%, respectively, and at the same time, the bio-available Cd decreased by 20.9-34.5%. Moreover, with the addition of GE, activities of urease and alkaline phosphatase increased in soil, while the peroxidase and superoxide dismutase activities were notably reduced in plants. Therefore, GE could be used as an effective amendment for the alleviation of Cd accumulation and toxicity, and thereby improve food safety.

Identification of Four Potential Biomarkers Associated With Coronary Artery Disease in Non-diabetic Patients by Gene Co-expression Network Analysis.

BACKGROUND: Coronary artery disease (CAD) is a type of cardiovascular disease that greatly hurts the health of human beings. Diabetic status is one of the largest clinical factors affecting CAD-associated gene expression changes. Most of the studies focus on diabetic patients, whereas few have been done for non-diabetic patients. Since the pathophysiological processes may vary among these patients, we cannot simply follow the standard based on the data from diabetic patients. Therefore, the prognostic and predictive diagnostic biomarkers for CAD in non-diabetic patient need to be fully recognized. MATERIALS AND METHODS: To screen out candidate genes associated with CAD in non-diabetic patients, weighted gene co-expression network analysis (WGCNA) was constructed to conduct an analysis of microarray expression profiling in patients with CAD. First, the microarray data GSE20680 and GSE20681 were downloaded from NCBI. We constructed co-expression modules via WGCNA after excluding the diabetic patients. As a result, 18 co-expression modules were screened out, including 1,225 differentially expressed genes (DEGs) that were obtained from 152 patients (luminal stenosis ≥50% in at least one major vessel) and 170 patients (stenosis of <50%). Subsequently, a Pearson's correlation analysis was conducted between the modules and clinical traits. Then, a functional enrichment analysis was conducted, and we used gene network analysis to reveal hub genes. Last, we validated the hub genes with peripheral blood samples in an independent patient cohort using RT-qPCR. RESULTS: The results showed that the midnight blue module and the yellow module played vital roles in the pathogenesis of CAD in non-diabetic patients. Additionally, CD40, F11R, TNRC18, and calcium/calmodulin-dependent protein kinase type II gamma (CAMK2G) were screened out and validated using enzyme-linked immunosorbent assay (ELISA) in an independent patient cohort and immunohistochemical (IHC) staining in an atherosclerosis mouse model. CONCLUSION: Our findings demonstrate that hub genes, CD40, F11R, TNRC18, and CAMK2G, are surrogate diagnostic biomarkers and/or therapeutic targets for CAD in non-diabetic patients and require deeper validation.

Potential of removing Cd(II) and Pb(II) from contaminated water using a newly modified fly ash.

Modified fly ash was prepared through low-temperature roasting method using NaOH as activator. The techniques of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray photoelectron spectroscopy (XPS) and the X-ray diffraction (XRD) were introduced to analyze the chemical and physical performance of samples, respectively. It was found that a significant improvements in activity and specific surface area of adsorbent. This work systematically reported the uptake performances of modified materials for single and two mixed toxic cations Pb(II) and Cd(II). The results unveiled that pseudo-second-order model was suitable to analyze the adsorption process. The adsorption process were better fitted by Langmuir model and the maximum uptake capacities were 126.55 and 56.31 mg g-1 for Pb(II) and Cd(II) in single system at 298 K, respectively. Additionally, in mixed solution, the maximum uptake capacity reduced to 120.48 and 36.10 mg g-1 under the same adsorption conditions. Competitive adsorption results demonstrated that adsorption ability was restricted by other metal ions, as while as, the binding affinity of two cations followed the order of Pb(II)>Cd(II). Meanwhile, the co-existed cations as Ca(II), Mg(II) Na(I) and K(I) had antagonistic effects on the uptake of Cd(II) and Pb(II). The results indicate that the modified fly ash was a low-cost and effective adsorbent for the cleaning up metal ions in wastewater, which has a promising application prospect.

Possibility of removing cadmium pollution from the environment using a newly synthesized material coal fly ash.

Coal fly ash (FA) is a solid waste produced in coal combustion. This study focused on the removal of Cd2+ from wastewater by a newly synthesized adsorbent material, the low-temperature and sodium hydroxide-modified fly ash (SHM-FA). The SEM and BET analyses of SHM-FA demonstrated that the adsorbent was porous and had a huge specific surface area. The XRF, XRD, FTIR and TGA characterization showed that SHM-FA has an amorphous structure and the Si-O and Al-O in the fly ash dissolved into the solution, which improved the adsorption capacity of Cd. The results indicated that SHM-FA has desired adsorption performance. The adsorption performance was significantly affected by the dosage, starting pH, Cd2+ initial concentrations, and temperature, as well as adsorption time. In the optimal conditions, the removal efficiency and adsorption capacity of Cd2+ by SHM-FA were 95.76% and 31.79 mg g-1, respectively. The experiment provided clearly explained adsorption kinetics and isotherms. And the results confirmed that the adsorption behavior was well described by the pseudo-second-order kinetic and Langmuir isotherm model, which means that the adsorption of Cd2+ was controlled by SHM-FA through surface reaction and external diffusion process. In addition, the recycling of SHM-FA for reuse after Cd2+ adsorption showed high removal efficiency up to six times of use. Therefore, it can be concluded that SHM-FA is a low-cost adsorbent for Cd2+ removal from wastewater.

Potentially Critical Roles of NDUFB5, TIMMDC1, and VDAC3 in the Progression of Septic Cardiomyopathy Through Integrated Bioinformatics Analysis.

Septic cardiomyopathy (SC) is a rare and harmful cardiovascular disease with decreased left ventricular (LV) output and multiple organ failure, which poses a serious threat to human life. Despite the advances in SC, its diagnostic basis and treatment methods are limited, and the specific diagnostic biomarkers and its candidate regulatory targets have not yet been fully established. In this study, the GSE79962 gene expression profile was retrieved, with 20 patients with SC and 11 healthy donors as control. Weighted gene coexpression network analysis (WGCNA) was employed to investigate gene modules that were strongly correlated with clinical phenotypes. Blue module was found to be most significantly related to SC. Moreover, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the coexpression genes in blue module and showed that it was associated with metabolic pathways, oxidative phosphorylation, and cardiac muscle contraction. Furthermore, a total of 10 hub genes NDUFB5, TIMMDC1, VDAC3, COQ10A, MRPL16 (mitochondrial ribosomal protein L16), C3orf43, TMEM182, DLAT, NDUFA8, and PDHB (pyruvate dehydrogenase E1 beta subunit) in the blue module were identified at transcriptional level and further validated at translational level in myocardium of an lipopolysaccharide-induced septic cardiac dysfunction mouse model. Overall, the results of quantitative real-time polymerase chain reaction were consistent with most of the microarray analysis results. Intriguingly, we observed that the highest change was NDUFB5, TIMMDC1, and VDAC3. These identified and validated genes provided references that would advance the understanding of molecular mechanisms of SC. Taken together, using WGCNA, the hub genes NDUFB5, TIMMDC1, and VDAC3 might serve as potential biomarkers for diagnosis and/or therapeutic targets for precise treatment of SC in the future.

B-type natriuretic peptide levels in patients with paroxysmal lone atrial fibrillation.

To investigate the levels of B-type natriuretic peptide (BNP) in patients with atrial fibrillation (AF) but without structural heart disease, we measured plasma BNP concentration in 61 consecutive AF patients and in 61 age- and sex-matched healthy subjects. Plasma BNP concentration in the AF group was significantly higher than in the control group (121+/-32 vs 41+/-12 pg/ml, P<0.001). Logistic regression analysis showed that age (r=0.66, P<0.001), left atrial diameter (r=0.59, P<0.01), and a history of AF (r=0.72, P<0.001) were independent predictors of elevated BNP. We concluded that BNP was elevated in patients with paroxysmal lone AF. The clinical significance of BNP elevation in these patients requires further investigation.

Catheter ablation of atrial fibrillation originating from superior vena cava.

Atrial fibrillation originating from rapid firing foci in the superior vena cava is rare. Its electrophysiological features and catheter ablation techniques are described in this report. A decapolar catheter was positioned in the superior vena cava to map the origin of the atrial fibrillation in a 39-year-old female patient who had a 3-year history of symptomatic atrial tachycardia and fibrillation. Intracardiac mapping showed rapid firing foci in the anterior wall of the superior vena cava (SVC), 2.0 cm above the SVC-right atrium junction. During tachycardia, the focal electrogram from SVC was 55 msec earlier than the P waves on body surface ECG. Radiofrequency catheter ablation successfully abolished SVC potentials, resulting in a SVC-atrium conduction block. There was no recurrence of atrial arrhythmia after a 14-month follow-up. Rapid activities from the muscle sleeves in the SVC may cause atrial fibrillation. Such a focal atrial fibrillation can be eliminated by isolating the arrhythmogenic SVC with radiofrequency catheter ablation.

Prolonged ventricular action potential duration due to nitric oxide release.

BACKGROUND: Our previous study has demonstrated that increased intracoronary perfusion leads to a flow-dependent inversion of T waves on body surface ECG. However, whether increased coronary flow influences ventricular action potential duration measured directly from myocardium is unknown. METHODS: In six pentobarbital-anesthetized sheep, fresh arterial blood was injected into the left circumflex coronary (LCX) artery at a rate of 6 and 10 mL/min, respectively, in the presence of normal coronary flow. Activation-recovery interval (ARI), an estimate of ventricular action potential duration, was measured from epicardial ECGs acquired from the LCX territory. RESULTS: The intracoronary injection prolonged ARI by an average of 21 +/- 9 and 33 +/- 14 msec, respectively. After pre-treatment with nitro-l-arginine, a nitric oxide synthase inhibitor, intracoronary injection at the rate of 6 and 10 mL/min lead to an ARI increase of 3 +/- 2 msec (p >0.05) and 11 +/- 6 msec (p <0.05) respectively. CONCLUSIONS: An increase in coronary flow prolongs ventricular action potential duration in the intact sheep heart. Nitric oxide mediates the injection-induced increase in action potential duration.

Long-term follow-up of patients with P-R prolongation after catheter ablation of slow pathway for atrioventricular node re-entrant tachycardia.

BACKGROUND: Long-term impact of interval between P wave and R wave (P-R) prolongation on prognosis of patients with successful catheter ablation of slow atrioventricular nodal pathway was investigated. METHODS: Among 436 patients undergoing slow-pathway ablation for atrioventricular node re-entrant tachycardia (AVNRT), 17 (3.9%) experienced permanent P-R prolongation. Ablation target sites where conduction block was induced were located in mid- or anteroseptum. Fast junctional rhythm with ventriculoatrial conduction block was observed in eight patients immediately before atrioventricular block. RESULTS: Antegrade slow-pathway conduction was eliminated in 16 patients, and retrograde fast- and slow-pathway conduction was abolished in all patients. There was no recurrence of AVNRT after an average of 38 +/- 12 month follow-up. There was no deterioration of atrioventricular block in these patients. Average PR interval prior to hospital discharge and at the end of follow-up was 0.24 +/- 0.02 sec and 0.23 +/- 0.02 sec, respectively (p >0.05). Left ventricular ejection fraction remained unchanged in these patients (p >0.05). CONCLUSIONS: Radiofrequency catheter ablation of slow pathway for AVNRT is associated with a small risk of atrioventricular block. PR prolongation after successful slow-pathway ablation is associated with benign prognosis.

Simplified approach to radiofrequency catheter ablation of paroxysmal supraventricular tachycardia.

AIM: To investigate the safety and efficacy of a simplified approach in radiofrequency catheter ablation of paroxysmal supraventricular tachycardia. METHODS: The study involved 239 patients (118 men and 121 women) with paroxysmal supraventricular tachycardia and normal 12-lead electrocardiographic (ECG) findings at sinus rhythm, who visited the Cardiology Department of Weifang Medical College Hospital between January 2000 and September 2003. The mean age of patients was 39.2+/-11.9 years. The patients were divided into two groups: one undergoing a conventional 5-catheter ablation (controls), and the other a simplified 3-catheter ablation (study group). The follow up after ablation lasted 12 months. No antiarrhythmic agents were prescribed to the patients with successful ablation. RESULTS: The conventional and the 3-catheter ablation group did not differ in ablation success (97.5% vs 98.3%, p=0.42) and recurrence of paroxysmal supraventricular tachycardia (2.5% vs 3.3%, p=0.23). The simplified approach was associated with a significantly shorter procedure duration (89.1+/-28.2 vs 96.1+/-21.2 minutes, p<0.01) and fluoroscopy time (10.7+/-2.6 vs 12.7+/-4.2 minutes, p<0.01). There were no significant differences between the two groups in the type and incidence of procedural complications and ablation success. CONCLUSIONS: The simplified 3-catheter ablation approach proved to be a safe and effective method for ablation of paroxysmal supraventricular tachycardia. However, further studies including larger sample of such patients are needed to assess the clinical outcomes and cost-effectiveness of this simplified procedure.