Assessment of Myofilament Ca<sup>2+</sup> Sensitivity Underlying Cardiac Excitation-contraction Coupling

Heart failure and cardiac arrhythmias are the leading causes of mortality and morbidity worldwide. However, the mechanism of pathogenesis and myocardial ...

Yan Bian University Hospital

To observe the situation of metabolic syndrome (MS) among Han-Chinese and Korean-Chinese in urban of Yanbian area.

[Investigation on the situation of metabolic syndrome among Han-Chinese and Korean-Chinese in urban of Yanbian area].

In this study, we discuss the influence of DNA strand length on DNA wrapping of single-walled carbon nanotubes under high-shear sonication and find that different strand length results in changed DNA-nanotube interaction, which is sensitively probed by the upshift extent of the Raman radial breathing mode bands of nanotubes due to DNA wrapping. The difference in the interaction between nanotubes and DNA strands of various length results in apparently different degrees of wrapping compactness, revealed by atomic force microscopy observations, and nanotube selectivity in wrapping, indicated by both Raman and photoluminescence spectroscopy results. The above findings can be utilized to precisely control the nanotube diameter distribution and modulate the physicochemical properties of the nanotube wrapped by DNA without any direct functionalization of nanotubes. This finding is of considerable interest from both theoretical and practical standpoints.

Loosening the DNA wrapping around single-walled carbon nanotubes by increasing the strand length.

Loss of polycystin-2 (PC2) in mice (Pkd2(-/-)) results in total body edema, focal hemorrhage, structural cardiac defects, abnormal left-right axis, hepatorenal and pancreatic cysts, and embryonic lethality. The molecular mechanisms by which loss of PC2 leads to these phenotypes remain unknown. We generated a model to allow targeted Pkd2 inactivation using the Cre-loxP system. Global inactivation of Pkd2 produced a phenotype identical to Pkd2(-/-) mice with undetectable PC2 protein and perinatal lethality. Using various Cre mouse lines, we found that kidney, pancreas, or time-specific deletion of Pkd2 led to cyst formation. In addition, we developed an immortalized renal collecting duct cell line with inactive Pkd2; these cells had aberrant cell-cell contact, ciliogenesis, and tubulomorphogenesis. They also significantly upregulated beta-catenin, axin2, and cMyc. Our results suggest that loss of PC2 disrupts normal behavior of renal epithelial cells through dysregulation of beta-catenin-dependent signaling, revealing a potential role for this signaling pathway in PC2-associated ADPKD.

Conditional mutation of Pkd2 causes cystogenesis and upregulates beta-catenin.

Descending vasa recta (DVR) are 12- to 15-μm microvessels that supply the renal medulla with blood flow. We examined the ability of intrinsic nitric oxide (NO) and reactive oxygen species (ROS) generation to regulate their vasoactivity. Nitric oxide synthase (NOS) inhibition with N(ω)-nitro-l-arginine methyl ester (l-NAME; 100 μmol/l), or asymmetric N(G),N(G)-dimethyl-l-arginine (ADMA; 100 μmol/l), constricted isolated microperfused DVR by 48.82 ± 4.34 and 27.91 ± 2.91%, respectively. Restoring NO with sodium nitroprusside (SNP; 1 mmol/l) or application of 8-Br-cGMP (100 μmol/l) reversed DVR vasoconstriction by l-NAME. The superoxide dismutase mimetic Tempol (1 mmol/l) and the NAD(P)H inhibitor apocynin (100, 1,000 μmol/l) also blunted ADMA- or l-NAME-induced vasoconstriction, implicating a role for concomitant generation of ROS. A role for ROS generation was also supported by an l-NAME-associated rise in oxidation of dihydroethidium that was prevented by Tempol or apocynin. To test whether H(2)O(2) might play a role, we examined its direct effects. From 1 to 100 μmol/l, H(2)O(2) contracted DVR whereas at 1 mmol/l it was vasodilatory. The H(2)O(2) scavenger polyethylene glycol-catalase reversed H(2)O(2) (10 μmol/l)-induced vasoconstriction; however, it did not affect l-NAME-induced contraction. Finally, the previously known rise in DVR permeability to (22)Na and [(3)H]raffinose that occurs with luminal perfusion was not prevented by NOS blockade. We conclude that intrinsic production of NO and ROS can modulate DVR vasoactivity and that l-NAME-induced vasoconstriction occurs, in part, by modulating superoxide concentration and not through H(2)O(2) generation. Intrinsic NO production does not affect DVR permeability to hydrophilic solutes.

Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction.

Shape controlled Au nanocrystal growth in ionic liquid has been studied by glow discharge plasma reduction. In an 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)]) solution with poly(vinyl pyrrolidone) (PVP) as surfactant, Au nanocrystals grow from faceted NPs to peanut-like particle aggregates, and eventually worm-like nanorods and nanowires as the growth time increases. This process is further found to be dependent on the concentration of employed surfactant. Based on systematic microscopic analysis and control experiments, a polymer-assisted oriented attachment mechanism is proposed to explain the observed morphologic evolution. Our work may have great implications for the employment of ionic liquids for shape controlled synthesis of nanocrystals.

Morphologic evolution of Au nanocrystals grown in ionic liquid by plasma reduction.

Pertussis is a highly contagious, respiratory disease associated with substantial morbidity and mortality. A rapid and reliable diagnostic method is essential for appropriate treatment and prevention. Expression profiles of circulating microRNAs (miRNAs) have been proven as new non-invasive biomarkers for infectious diseases. We aimed to investigated the serum miRNA profile in pertussis patients and explored its potential as a novel diagnostic biomarker for pertussis. Among 664 different miRNAs analyzed using a miRNA array, 50 were overexpressed and 81 were underexpressed in the serum of pertussis patients. Expression levels of seven candidate miRNAs were further evaluated by real-time qRT-PCR. A panel of five miRNAs (miR-202, miR-342-5p, miR-206, miR-487b, miR-576-5p) was confirmed overexpressed in pertussis patients (p < 0.05). Risk score and receiver-operating characteristic (ROC) analysis showed that the area under the curve of the five-member miRNA profile was 0.980. At an optimal cutoff value (0.707), this panel of miRNAs yielded a sensitivity of 97.4 % and a specificity of 94.3 %. These data suggest that the five-member serum miRNA profile may serve as a new biomarker for pertussis diagnosis with high specificity and sensitivity.

Serum microRNA expression profile as a biomarker for the diagnosis of pertussis.

Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection.

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection.

Cathepsin K is a potent collagenase implicated in human and animal atherosclerosis-based vascular remodeling. This study examined the hypothesis that serum CatK is associated with the prevalence of coronary artery disease (CAD).

Increased serum cathepsin K in patients with coronary artery disease.

As a promising material for photoelectrical application, MoS2 has attracted extensive attention on its facile synthesis and unique properties. Herein, we explored a novel strategy of laser ablation to synthesize MoS2 fullerene-like nanoparticles (FL-NPs) with stable photoresponse under high temperature. Specifically, we employed a millisecond pulsed laser to ablate the molybdenum target in dimethyl trisulfide gas, and as a result, the molybdenum nanodroplets were ejected from the target and interacted with the highly reactive ambient gas to produce MoS2 FL-NPs. In contrast, the laser ablation in liquid could only produce core-shell nanoparticles. The crucial factors for controlling final nanostructures were found to be laser intensity, cooling rate, and gas reactivity. Finally, the MoS2 FL-NPs were assembled into a simple photoresponse device which exhibited excellent thermal stability, indicating their great potentialities for high-temperature photoelectrical applications.

Millisecond laser ablation of molybdenum target in reactive gas toward MoS2 fullerene-like nanoparticles with thermally stable photoresponse.

Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the "lowLVEF" group) and the 90 patients showing LVEF values ≥ 40% (the "highLVEF" group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = -0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84-0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF.

Increased Circulating Cathepsin K in Patients with Chronic Heart Failure.

A novel non-enzymatic glucose sensor based on a glassy carbon electrode modified with Pt3Ru1 alloy nanoparticles (Pt3Ru1/GCE) was fabricated. Pt3Ru1 alloy nanoparticles were prepared by a reverse microemulsion method at room temperature. The X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) demonstrate that Pt3Ru1 nanoparticles are disordered alloy with face central cubic (fcc) structure and the atom ratio of Pt and Ru is 3:1. The high-resolution transmission electron microscopy (HRTEM) images show that Pt3Ru1 alloy nanoparticles were aggregated with a high density of surface defects. Furthermore, the sensor properties of Pt3Ru1/GCE were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA) in 0.01 M PBS (pH 7.4). The results indicate that the proposed sensor exhibits a wide linear range of 5 × 10(-7)M to 10(-2)M (R(2)=0.9988) with a low detection limit of 0.3 μM for glucose. Moreover, the sensor demonstrates good sensitivity, stability, reproducibility, and better anti-interference performance toward ascorbic acid (AA), uric acid (UA), and fructose (Fru).

A novel non-enzymatic glucose sensor based on Pt3Ru1 alloy nanoparticles with high density of surface defects.

Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the increased lung cancer risk in populations, but the mechanisms underlying PM-associated carcinogenesis are not yet clear. Previous studies have indicated that aberrant epigenetic alterations, such as genome-wide DNA hypomethylation and gene-specific DNA hypermethylation contribute to lung carcinogenesis. And silence or mutation of P53 tumor suppressor gene is the most prevalent oncogenic driver in lung cancer development. To explore the effects of PM2.5 on global and P53 promoter methylation changes and the mechanisms involved, we exposed human bronchial epithelial cells (BEAS-2B) to low concentrations of PM2.5 for 10 days. Our results indicated that PM2.5-induced global DNA hypomethylation was accompanied by reduced DNMT1 expression. PM2.5 also induced hypermethylation of P53 promoter and inhibited its expression by increasing DNMT3B protein level. Furthermore, ROS-induced activation of Akt was involved in PM2.5-induced increase in DNMT3B. In conclusion, our results strongly suggest that repeated exposure to PM2.5 induces epigenetic silencing of P53 through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation, which not only provides a possible explanation for PM-induced lung cancer, but also may help to identify specific interventions to prevent PM-induced lung carcinogenesis.

Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation.

Mitochondrial dysfunction has been implicated in acute, severe liver injury caused by overdose of acetaminophen (APAP). However, whether mitochondrial biogenesis is involved is unclear. Here we demonstrated that mitochondrial biogenesis, as indicated by the amounts of mitochondrial DNA and proteins, increased significantly in HepG2 cells exposed to low, non-cytotoxic concentrations of APAP. This heightened response was accompanied by upregulated expression of PGC-1α, NRF-1 and TFAM, which are key transcriptional regulators of mitochondrial biogenesis. Additionally, antioxidants including glutathione, MnSOD, HO-1, NQO1, and Nrf2 were also significantly upregulated. In contrast, for HepG2 cells exposed to high, cytotoxic concentration of APAP, mitochondrial biogenesis was inhibited and the expression of its regulatory proteins and antioxidants were concentration-dependently downregulated. In summary, our study indicated that mitochondrial biogenesis, along with antioxidant induction, may be an important cellular adaptive mechanism counteracting APAP-induced toxicity and overwhelming this cytoprotective capacity could result in liver injury.

Lan Cui

Yan Bian University Hospital

Assessment of Myofilament Ca²⁺ Sensitivity Underlying Cardiac Excitation-contraction Coupling

Lan Cui

Yan Bian University Hospital

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling

Assessment of Myofilament Ca²⁺ Sensitivity Underlying Cardiac Excitation-contraction Coupling