Myocardial Injury in Rats Exposed to High-Intensity Exercise Evaluated by 2-D Speckle Tracking Imaging.

OBJECTIVE: The aim of the work described here was to evaluate strain and morphological change of the left ventricle in Sprague Dawley (SD) rats at different exercise intensities by 2-D speckle tracking imaging (STI). METHODS: Seventy-two 8-wk-old SD rats were divided into four groups on the basis of exercise intensity: sedentary (SED), low-intensity running, medium-intensity running (MIR) and high-intensity running (HIR). Each group was further sub-divided into three groups of different exercise lengths: 1, 4 and 8 wk. The structural measurements of the left ventricle and left ventricular ejection fraction (LVEF) were obtained by echocardiography. Systolic peak values of global longitudinal, circumferential and radial strains (GLS, GCS and GRS) were obtained. Histopathological results of the cross-sectional area (CSA) of myocardial cells, collagen volume fraction (CVF) of the myocardium and perivascular collagen area (PVCA) were also observed. RESULTS: Structural measurements of the left ventricle and LVEF did not change with different exercise intensities or lengths. GLS of the HIR8 wk sub-group was significantly lower than those of the SED8 wk and MIR8 wk sub-groups. Conversely, the GLS and GCS of the HIR8 wk sub-group were lower than those of the HIR1 wk and HIR4 wk sub-groups. Histopathologically, the CSA of myocardial cells significantly increased across all HIR sub-groups and the MIR4 wk and MIR8 wk sub-groups. CVFendo and PVCA were also significantly increased in the HIR4 wk and HIR8 wk sub-groups. The HIR8 wk group also had regional swelling and ill-defined boundaries of myocardial cells. CONCLUSION: Prolonged, high-intensity exercise may lead to exercise-induced injury of the myocardium. Two-dimensional STI can be used as a non-invasive early detection method for exercise-induced injury of myocardial function, compared with LVEF.

[Adverse cardiovascular effects of antiretrovirals in female mice during gestation].

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

Simulation on oily contamination removal by ozone using molecular dynamics.

Ozone (O3) is characteristic of high oxidative activity. It displays a high potential value in sterilization and decontamination. Although O3 has been widely investigated for its efficiency and environmentally friendly effectiveness, the fundamental issue regarding the complicated microscopic interaction mechanism between O3 and contaminant molecules remains largely unaddressed. We addressed this knowledge gap through molecular dynamics (MD) simulation at the molecular scale. Results indicated that five representative hydrocarbon molecules (n-hexadecane, phytane, terpane, naphthalin and acenaphthylene) on a rough silica (SiO2) surface were almost removed after about 300 ps simulation. And the aromatic molecules were easier to be removed than aliphatic ones. The hydroxyl oxidation reaction was demonstrated as a predominant mechanism. As the large dose of O3 was supplied by atmospheric air dielectric barrier discharge (DBD) plasma, this work provided an important theoretical reference for better using plasma technology for oily contaminant removal.

Circular RNAs in liver diseases: Mechanisms and therapeutic targets.

Circular RNAs (circRNAs) are formed from the genome through diverse back splicing and feature the closed loop. circRNAs are widely available in a variety of cells and characterized by conservation, structural stability, high abundance and tissue-specific or developmental-specific expression. Recent studies have shown that circRNAs are closely related to liver diseases, such as metabolic-associated fatty liver disease, hepatitis, liver cirrhosis and hepatocellular carcinoma. circRNAs play an important role in the progression of liver diseases, are potential diagnostic and prognostic markers, and have translational value in therapy. This article reviews the research on circRNAs in liver diseases, with a view to providing a theoretical basis and new ideas for future research and treatment of liver diseases.

Characterization of complex fluvio-deltaic deposits in Northeast China using multi-modal machine learning fusion.

Due to the lack of petroleum resources, stratigraphic reservoirs have become an important source of future discoveries. We describe a methodology for predicting reservoir sands from complex reservoir seismic data. Data analysis involves a bio-integrated framework called multi-modal machine learning fusion (MMMLF) based on neural networks. First, acoustic-related seismic attributes from post-stack seismic data were used to characterize the reservoirs. They enhanced the understanding of the structure and spatial distribution of petrophysical properties of lithostratigraphic reservoirs. The attributes were then classified as varied modal inputs into a central fusion engine for prediction. We applied the method to a dataset from Northeast China. Using seismic attributes and rock physics relationships as input data, MMMLF was performed to predict the spatial distribution of lithology in the Upper Guantao substrata. Despite the large scattering in the acoustic-related data properties, the proposed MMMLF methodology predicted the distribution of lithological properties through the gamma ray logs. Moreover, complex stratigraphic traps such as braided fluvial sandstones in the fluvio-deltaic deposits were delineated. These findings can have significant implications for future exploration and production in Northeast China and similar petroleum provinces around the world.

On the nonlinear temperature dependence of elastic constants and wave velocities for solid media with applications to geologic materials.

Temperature-induced variations of elastic moduli in solid media are generally characterized by a strong nonlinear dependence on temperature associated with complex deformations under thermal treatments. Conventional thermoelasticity with third-order elastic constants for the one-order temperature dependence has been extensively studied for crystals, but encountering problems of divergent and limited velocity variations for rocks as a polycrystal mixture, especially at high temperatures. The extension of the theory beyond high-order elastic constants to solid media is addressed in this article to describe the nonlinear temperature dependence of both elastic constants and wave velocities. The total strain is divided into the background component associated with temperature variations and the infinitesimal component induced by propagating waves. A third-order temperature dependence of velocity variations is formulated by taking into account fourth-order elastic constants. Applications to solid rocks (sandstone, granite, and olivine) demonstrate an accurate description of temperature-induced variations, especially for high temperatures. Unlike crystals, the synthetic averaging elastic constants for a solid rock (as a polycrystal mixture) change less than 10% with temperatures. The thermal sensitivity of P-wave velocities is much more than that of S-wave velocities over the vast majority of temperatures examined.

Poro-acoustoelastic constants based on Padé approximation.

Stress-induced velocity variations for porous rocks are generally characterized by a strong nonlinear dependence on stress associated with complex deformations under loading. The classical theory of poro-acoustoelasticity with high-order elastic constants is based on the Taylor expansion of the strain energy function, encountering problems of divergence and limitless elastic wave velocities in describing stress-associated velocity variations, especially for high effective stresses. The extension of the theory beyond the high-order elastic constants based on the Padé approximation to the strain energy function is addressed in this article. The resultant acoustoelastic constants are characteristics of a reasonable theoretical limit in elastic wave velocities with increasing effective stresses, avoiding some of the problems associated with high-order elastic constants such as decreasing moduli with increasing effective pressure at high effective pressure, possibly implying the microstructural dependence of elastic constants. That is, the loading stress increases strain energy and wave velocity, but also induces frame-related attenuation, which in turn reduces stiffness and elastic constants. The Padé nonlinear constants can be reduced for low effective stresses to the conventional acoustoelastic constants based on the Taylor expansion. Theoretical results are compared with ultrasonic measurements for a perfectly elastic crystal, topaz (Al2SiO4F2), and a porous rock, demonstrating that the Padé-approximation-based acoustoelasticity gives a more accurate description of stress-associated velocity variations, especially for higher effective stresses.

Plumbagin Ameliorates CCl 4 -Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway.

Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4 treated rats. At concentrations of 2 to 6 µM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF-like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression of α-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells.

The prognostic significance of preoperative plasma levels of osteopontin in patients with TNM stage-I of hepatocellular carcinoma.

PURPOSE: To evaluate the prognostic value of preoperative plasma osteopontin (OPN) levels in patients with early stage of hepatocellular carcinoma (HCC). METHODS: Preoperative plasma levels of OPN were detected by ELISA in 68 patients with tumor-node metastasis system stage-I of HBV-related HCC, and their association with tumor recurrence or patients' survival was analyzed. RESULTS: The median plasma OPN level of patients was 82.51 ng/ml (25­75% interquartile range, 63.15­110.45 ng/ml). Plasma OPN levels in patients with tumor size C5 cm in diameter were significantly higher than that of patients with tumor size\5 cm in diameter (104.76 vs.75.16 ng/ml, P = 0.003). When the 100 ng/ml was used asa cut-off value to divide the patients into two groups: the higher plasma OPN group and the lower plasma OPN group, the tumor recurrence rate of the higher plasma OPN group was significantly higher than that of the lower plasma OPN group (52.17 vs. 24.44%, P = 0.022). Meanwhile, the recurrence rate of the patients with positive alpha fetoprotein (AFP) (45.5%) was significantly higher than that of those negative AFP patients (12.5%,P = 0.006). A higher plasma OPN level was one leading independent prognostic factor for both overall survival(OS) and relapse-free survival in multivariate Cox models. CONCLUSION: The preoperative plasma OPN level and serum AFP level in patients with early stage of HCC can be used as a prognostic marker for early stage of HCC.

[Identification of metastasis-related microRNAs of hepatocellular carcinoma in hepatocellular carcinoma cell lines by quantitative real time PCR].

OBJECTIVE: To identify the metastasis-related miRNAs in hepatocellular carcinoma (HCC) cell lines. METHODS: A qRT-PCR method was established and optimized. RESULTS: All candidate metastasis associated miRNAs except miR-124a were expressed in high metastasis cell line MHCC97H and low metastasis cell line MHCC97L, while some miRNAs were differentially expressed between liver cancer cell line (HepG2) and hepatic cell line (L02) (P less than 0.05), these miRNAs include: miR-148b (1.96+/-0.51 vs 3.76+/-0.28), miR-9 (-4.38+/-0.86 vs -1.10+/-0.53), miR-30c (8.41+/-0.40 vs 6.82+/-0.29), miR-338 (3.14+/-0.29 vs -2.36+/-0.32), miR-34a (0.71+/-0.40 vs -2.95+/-0.26), Let-7g (-4.07+/-0.55 vs -6.98+/-0.56). miR-148b expression was about 4 times higher than miR-148a [5.46 (IQR 4.25-6.67) vs 1.29 (IQR 0.94-1.64)] in all cell line tested (Z=-5.097, P=3x10(-7)). CONCLUSION: This study may help to understand the biological significance of miRNAs in HCC metastasis.

Suitable reference genes for real-time PCR in human HBV-related hepatocellular carcinoma with different clinical prognoses.

BACKGROUND: Housekeeping genes are routinely used as endogenous references to account for experimental differences in gene expression assays. However, recent reports show that they could be de-regulated in different diseases, model animals, or even under varied experimental conditions, which may lead to unreliable results and consequently misinterpretations. This study focused on the selection of suitable reference genes for quantitative PCR in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different clinical outcomes. METHODS: We evaluated 6 commonly used housekeeping genes' expression levels in 108 HBV-related HCCs' matched tumor and non-tumor tissue samples with different clinical outcomes and 26 normal liver specimens by real-time PCR. The expression stability of the 6 genes was compared using the software programs geNorm and NormFinder. To show the impact of reference genes on data analysis, we took PGK1 as a target gene normalized by each reference gene, and performed one-way ANOVA and the equivalence test. RESULTS: With the geNorm and NormFinder software programs, analysis of TBP and HPRT1 showed the best stability in all tissue samples, while 18s and ACTB were less stable. When 18s or ACTB was used for normalization, no significant difference of PGK1 expression (p > 0.05) was found among HCC tissues with and without metastasis, and normal liver specimens; however, dramatically differences (p < 0.001) were observed when either TBP or the combination of TBP and HPRT1 were selected as reference genes. CONCLUSION: TBP and HPRT1 are the most reliable reference genes for q-PCR normalization in HBV-related HCC specimens. However, the well-used ACTB and 18S are not suitable, which actually lead to the misinterpretation of the results in gene expression analysis.