Association Between the Lipid Profile and Renal Dysfunction in the Heart Failure Patients.

BACKGROUND/AIMS: In heart failure patients with high prevalence of chronic renal disease (CKD), hospitalization and mortality, whether the lipid profile was associated with renal dysfunction remained unknown. The present study intended to clarify the association between the lipid profile and renal dysfunction in the heart failure patients. METHODS: 336 hospitalized heart failure patients with left ventricle ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. The estimated glomerular filtration rate (eGFR) < 90 mL/min·1.73 m2 was defined as renal dysfunction. The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with eGFR. The significantly correlated factors were enrolled in Logistic regression as confounding factors to determine the association between the lipid profile and renal dysfunction in the heart failure patients. RESULTS: 182 patients (54.2%) had renal dysfunction and 154 patients (45.8%) did not have renal dysfunction. The waist circumference, platelet counts, platelet distribution width (PDW), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1), albumin and left ventricular ejection fraction (LVEF) are positively correlated with eGFR (all P< 0.05). Meanwhile, the age, mean platelet volume (MPV), neutrophilic granulocyte percentage (NEUT%), urea nitrogen (BUN), creatinine and total bilirubin (TBIL) are negatively correlated with eGFR (all P< 0.05). The total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) show no correlation with eGFR. After the adjustment of sex, hypertension, diabetes mellitus, age, waist circumference, platelet counts, MPV, PDW, NEUT%, TBIL, albumin and LVEF, HDL-C is the only lipid factor still significantly associated with renal dysfunction in hospitalized heart failure patients (OR=0.119, P=0.003). CONCLUSION: Among the lipid profile of TC, triglyceride, LDL-C, HDL-C, apo A1 and apo B, the HDL-C is the only lipid factor significantly associated with renal dysfunction in hospitalized heart failure patients.

Emerging Roles of Histidine Triad Nucleotide Binding Protein 1 in Neuropsychiatric Diseases.

The histidine triad nucleotide binding protein1(HINT1),which belongs to the histidine triad(HIT) enzyme superfamily,exerts its enzymic activities as hydrolase or transferase. Its physiological functions are still unclear. HINT1 protein is expressed in various tissues and plays an important role in transcription and signal transduction. Earlier studies have identified HINT1 as a haplo-insufficient tumor suppressor. Other evidences indicate that HINT1 is involved in a wide variety of physiological processes,some of which are irrelevant with its basic enzymic activities. Investigations recently suggest that HINT1 is closely related to many peripheral and central nervous system diseases,and plays a vital role in some of neuropsychiatric diseases such as inherited peripheral neuropathies,schizophrenia,mood disorder,drug addiction,and Down's syndrome. In this review,the role of HINT1 in above-mentioned neuropsychiatric disorders was summarised,and the research findings of HINT1 in each of the above diseases were summarized and analyzed,in order to provide some guidance for further research on this protein.

Association between neutrophilic granulocyte percentage and depression in hospitalized patients with heart failure.

BACKGROUND: Previous researches reveal that depression is associated with increased inflammatory markers. As a simple and cheap inflammatory marker, we hypothesize that neutrophilic granulocyte percentage is associated with depression in hospitalized heart failure patients, whose prevalence of depression is at a very high level. METHODS: Three hundred sixty-six cases of hospitalized heart failure patients with left ventricular ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. All the enrolled patients received Hamilton Rating Scale for Depression (24-items) (HAM-D24). The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with HAM-D24 depression index. The significantly correlated factors were enrolled as independent variables in Logistic regression to determine the risk or protective factors for depression, which was taken as dependent variable. RESULTS: Two hundred ten cases of hospitalized heart failure patients (57.4%) had depression. Among them, 134 patients (63.8%) had mild depression, 58 patients (27.6%) had moderate depression and 18 patients (8.6%) had severe depression. Pearson simple linear correlation revealed that in hospitalized patients with heart failure, the neutrophils granulocyte percentage was positively correlated with the HAM-D24 depression index (r = .435, p < .001). After the adjustment of age, BMI, number of members of the household, smoking index, New York Heart Association (NYHA) classification, hemoglobin, TC, LDL-C, creatinine, cystatin-C, TBIL and albumin, the neutrophils granulocyte percentage is still significantly associated with depression in hospitalized heart failure patients (OR = 1.046, p < .001). CONCLUSIONS: The neutrophils granulocyte percentage may be used as a new marker for depression in hospitalized heart failure patients.

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

AIM: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. METHODS: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. RESULTS: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. CONCLUSION: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

[Histidine triad nucleotide-binding protein 1 and human diseases].

Histidine triad nucleotide-binding protein 1 (HINT1) is a member of a superfamily of histidine triad proteins named by the conserved nucleotide-binding motif histidine-x-histidine-x-histidine-xx, in which x represents hydrophobic amino acid. HINT1 is implicated in pathological progress of many human diseases including cancer and schizophrenia; however, little is known about the essential role and pathological consequences of HINT1 in cellular physiology and diseases. Therefore, we summarize the structure, distribution, and physiological function of HINT1 in cells and tissues as well as the correlation between HINT1 and human diseases.

Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy.

BACKGROUND: Endoplasmic reticulum (ER) stress is considered one of the mechanisms contributing to reactive oxygen species (ROS)-mediated cell apoptosis. In diabetic cardiomyopathy (DCM), cell apoptosis is generally accepted as the etiological factor and closely related to cardiac ROS generation. ER stress is proposed the link between ROS and cell apoptosis; however, the signaling pathways and their roles in participating ER stress-induced apoptosis in DCM are still unclear. METHODS: In this study, we investigated the signaling transductions in ROS-dependent ER stress-induced cardiomocyte apoptosis in animal model of DCM. Moreover, in order to clarify the roles of IRE1 (inositol-requiring enzyme-1), PERK (protein kinase RNA (PKR)-like ER kinase) and ATF6 (activating transcription factor-6) in conducting apoptotic signal in ROS- dependent ER stress-induced cardiomocyte apoptosis, we further investigated apoptosis in high-glucose incubated cardiomyocytes with IRE1, ATF6 and PERK-knocked down respectively. RESULTS: we demonstrated that the ER stress sensors, referred as PERK, IRE1 and ATF6, were activated in ROS-mediated ER stress-induced cell apoptosis in rat model of DCM which was characterized by cardiac pump and electrical dysfunctions. The deletion of PERK in myocytes exhibited stronger protective effect against apoptosis induced by high-glucose incubation than deletion of ATF6 or IRE in the same myocytes. By subcellular fractionation, rather than ATF6 and IRE1, in primary cardiomyocytes, PERK was found a component of MAMs (mitochondria-associated endoplasmic reticulum membranes) which was the functional and physical contact site between ER and mitochondria. CONCLUSIONS: ROS-stimulated activation of PERK signaling pathway takes the major responsibility rather than IRE1 or ATF6 signaling pathways in ROS-medicated ER stress-induced myocyte apoptosis in DCM.

Enhanced expression of MYF5 and MYOD1 in fibroblast cells via the forced expression of bos taurus MYF5.

The formation of vertebrate skeletal muscles widely thought to be under the control of hierarchy of regulatory genes. MYF5 is one of the myogenic determination gene expressed in the developing mouse dermomyotome which control skeletal muscle differentiation. In the current work, we had obtained the cDNA sequence including the full coding region of the bos taurus myogenic factor MYF5 by reverse transcription polymerase chain reaction. Furthermore, we examined whether fibroblast cell derived from mouse and bos taurus can be transduced using plasmid vectors carrying bos taurus MYF5. Bos taurus MYF5 activates MYF5 and MYOD1 expression after 1 day culture. The concerted upregulation of the myogenic regulatory factors enhanced myosin (skeletal fast) expression. These observation show that MYF5 is essential for myogenic differentiation and provides candidates for regulation bos taurus skeletal muscle development.

[Determination of electron density in atmospheric pressure radio frequency dielectric barrier discharges by Stark broadening].

The use of high frequency power to generate plasma at atmospheric pressure is a relatively new development. An apparatus of atmospheric pressure radio frequency dielectric barrier discharge was constructed. Plasma emission based measurement of electron density in discharge columns from Stark broadening Ar is discribed. The spacial profile of electron density was studied. In the middle of the discharge column, as the input power increases from 138 to 248 W, the electron density rises from 4.038 x 10(21) m(-3) to 4.75 x 10(21) m(-3).

Hamilton rating scale for depression-24 (HAM-D24) as a novel predictor for diabetic microvascular complications in type 2 diabetes mellitus patients.

The study was designed to investigate whether the hamilton rating scale for depression (24-items) (HAM-D24) can be used to predict the diabetic microvascular complications in type 2 diabetes mellitus (T2DM) patients. 288 hospitalized patients with T2DM were enrolled. Their diabetic microvascular complications including diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy and diabetic foot as well as demographic, clinical data, blood samples and echocardiography were documented. All the enrolled patients received HAM-D24 evaluation. The HAM-D24 score and incidence of depression in T2DM patients with each diabetic microvascular complication were significantly higher than those in T2DM patients without each diabetic microvascular complication. After the adjustment of use of insulin and hypoglycemic drug, duration of T2DM, mean platelet volume, creatinine, albumin, fasting glucose, glycosylated hemoglobin type A1C, left ventricular ejection fraction, respectively, HAM-D24 score was still significantly associated with diabetic microvascular complications (OR = 1.188-1.281, all P < 0.001). The AUC of HAM-D24 score for the prediction of diabetic microvascular complication was 0.832 (0.761-0.902). 15 points of HAM-D24 score was considered as the optimal cutoff with the sensitivity of 0.778 and specificity of 0.785. In summary, HAM-D24 score may be used as a novel predictor of diabetic microvascular complications in T2DM patients.

G-T haplotype established by rs3785889-rs16941382 in GOSR2 gene is associated with coronary artery disease in Chinese Han population.

OBJECTIVES: The aim of the present study is to assess the association between the human GOSR2 gene and coronary artery disease using a haplotype-based case-control study in Chinese Han population. METHODS: A total of 283 coronary artery disease patients and 280 controls were genotyped for the human GOSR2 gene (rs197932, rs3785889, rs197922, rs17608766, and rs16941382). Data were analyzed for three separate groups: the total subjects, men, and women. RESULTS: For the total subjects, the frequency of the G-T haplotype established by rs3785889-rs16941382 was significantly higher in the coronary artery disease patients as compared to the control subjects (P=0.009). Multiple logistic regression analysis also confirmed that the subjects with G-T haplotype established by rs3785889-rs16941382 (homozygote) were found having significantly higher chance suffering from coronary artery disease than the ones without this haplotype (OR=1.887, P=0.007). CONCLUSIONS: The G-T haplotype established by rs3785889-rs16941382 may be a risk genetic marker for coronary artery disease patients in Chinese Han population.

[Spectroscopic measurements of atomic hydrogen concentrations in dielectric barrier discharge hydrogen plasmas].

Atomic hydrogen plays important roles in chemical vapor deposition of functional materials, plasma etching, and surface cleaning. The present work introduces the fundamental principle to determine atomic hydrogen density via optical emission spectroscopy using Ar as an actinometer, and also reports the experimental results of atomic hydrogen density in the DBD discharge hydrogen plasmas. The variations of atomic hydrogen density and the hydrogen dissociation fraction as a function of pressure were calculated based on some of the available electron-impact excitation cross section and quenching cross sections in the literatures. In this work, as the pressure increases from 0.32 to 5.1 kPa, the hydrogen dissociation fraction decreases from 5.2% to 0.089%, and the atomic hydrogen density decreases from 4.9 x 10(15) cm(-3) to 1.3 x 10(15) cm(-3). The variations of H atom Balmer lines and Ar (750.4 nm) emission intensity as functions of gas pressure, discharge voltage, and frequency were also investigated.

Zirconium oxide ceramic foam: a promising supporting biomaterial for massive production of glial cell line-derived neurotrophic factor.

This study investigated the potential application of a zirconium oxide (ZrO2) ceramic foam culturing system to the production of glial cell line-derived neurotrophic factor (GDNF). Three sets of ZrO2 ceramic foams with different pore densities of 10, 20, and 30 pores per linear inch (PPI) were prepared to support a 3D culturing system. After primary astrocytes were cultured in these systems, production yields of GDNF were evaluated. The biomaterial biocompatibility, cell proliferation and activation of cellular signaling pathways in GDNF synthesis and secretion in the culturing systems were also assessed and compared with a conventional culturing system. In this study, we found that the ZrO2 ceramic foam culturing system was biocompatible, using which the GDNF yields were elevated and sustained by stimulated cell proliferation and activation of signaling pathways in astrocytes cultured in the system. In conclusion, the ZrO2 ceramic foam is promising for the development of a GDNF mass production device for Parkinson's disease treatment.

Selenium deficiency is associated with endoplasmic reticulum stress in a rat model of cardiac malfunction.

The relationship between selenium (Se) deficiency-induced cardiac malfunction and endoplasmic reticulum (ER) stress is poorly understood. In the present study, 18 weaning Sprague Dawley rats were randomly fed with three different Se diets, and myocardial glutathione peroxidase (GPx) activity was measured by an enzyme activity assay. Cardiac function was evaluated by hemodynamic parameters. ER stress markers immunoglobulin-binding protein (BiP)/glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were detected by western blotting. Our data showed that myocardial GPx activity and cardiac function were conspicuously impaired in Se-deficient rats. Expression of GRP78 and CHOP was significantly upregulated by treatment of Se deficiency. Improvements in myocardial GPx activity and cardiac function, as well as decreases in expression of GRP78 and CHOP, were observed after Se supplementation. Consequently, our data show that ER stress was involved in Se deficiency-induced cardiac dysfunction.

Selenium attenuates high glucose-induced ROS/TLR-4 involved apoptosis of rat cardiomyocyte.

The potential mechanism of high glucose-induced cardiomyocyte apoptosis and selenium's protective effects were investigated in this study. Myocytes isolated from neonate rats were cultured in high-glucose medium (25.5 mmol/L glucose) to mimic sustained hyperglycemia. Before high-glucose incubation, myocytes were pretreated by sodium selenite solution. Cell apoptosis was evaluated by annexin V/propidium iodide (PI) staining and caspase activation. Expression of Toll-like receptor 4 (TLR-4) and myeloid differentiation factor 88 (MyD-88) was examined at both mRNA and protein levels. The intracellular reactive oxygen species (ROS) production and glutathione peroxidase (GPx) activity in myocytes were also detected. We found high glucose-induced cell apoptosis and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling, accompanied by increased production of ROS. Selenium pretreatment attenuated apoptosis in high glucose-incubated myocytes, and mechanically, this protective effect was found to be associated with attenuating oxidative status by increasing activity of GPx, decreasing the generation of ROS, as well as inhibition of the activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling in myocytes. These results suggest that activation of TLR-4/MyD-88 signaling pathway plays an important role in high glucose-induced cardiomyocyte apoptosis. Additionally, by modulating TLR-4/MyD-88 signaling pathway, which is linked to ROS formation, selenium exerts its antioxidative and antiapoptotic effects in high glucose-incubated myocytes.

Selenium attenuates adriamycin-induced cardiac dysfunction via restoring expression of ATP-sensitive potassium channels in rats.

The possible mechanism of adriamycin (ADR) and/or selenium (Se) deficiency-induced cardiac dysfunction, and cardioprotective effects of Se against ADR-induced cardiac toxicity were investigated in this study. Cardiac function was evaluated by plasma brain natriuretic peptide level and echocardiographic and hemodynamic parameters. Cardiac glutathione peroxidase (GPx) activity was assessed spectrophotometrically. Expression of ATP-sensitive potassium channels (KATP) subunits-SUR2A and Kir6.2-were examined by real-time PCR and Western blotting. The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co-administration of ADR and Se deficiency. Mechanically, it is novel for us to find down-regulation of KATP subunits gene expression in cardiac tissue after administration of ADR or Se deficiency, and more significant inhibition of cardiac KATP gene expression was identified after co-administration of ADR and Se deficiency. Furthermore, cardiac toxicity of ADR was found alleviated by Se supplementation, accompanied by restoring of cardiac GPx activity and cardiac KATP gene expression. These results indicate that decreased expression of cardiac KATP is involved in adriamycin and/or Se deficiency-induced cardiac dysfunction; Se deficiency exacerbates adriamycin-induced cardiac dysfunction by future inhibition of KATP expression; Se supplementation seems to protect against adriamycin-induced cardiac dysfunction via restoring KATP expression, showing potential clinical application in cancer chemotherapy.

Chrysanthemum indicum ethanolic extract inhibits invasion of hepatocellular carcinoma via regulation of MMP/TIMP balance as therapeutic target.

Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and postsurgical recurrence. Thus, the inhibition of invasion and metastasis is of great importance in its therapies. Medicinal plants or ethnopharmacology used in folklore medicine continue to be an important source of discovery and development of novel or potential therapeutic agents for treatment of cancer. Chrysanthemum indicum, one of the medicinal plants or ethnopharmacology, is being used for treatment of many diseases including cancer. However, this plant molecular mechanisms underlining the anti-metastatic effects have not been well documented. In this study, Chrysanthemum indicum ethanolic extract (CIE) significantly suppressed proliferation and invasion of MHCC97H cells, one of the HCC cell lines with high metastatic potential, in a dose-dependent manner. CIE markedly decreased MMP-2 and MMP-9 expression, increased simultaneously TIMP-1, and TIMP-2 expression further restoring their balance in the cancer cells. The present study indicates that CIE reduced MHCC97H cell metastatic capability, in part at least, through decrease of the MMP expression, simultaneous increase of the TIMP expression, further restoring their balance as therapeutic target in HCC. It is suggested that Chrysanthemum indicum is a potential novel therapeutic medicinal plant for treatment of HCC or cancer invasion and metastasis.

Changes of splenic macrophage during the process of liver cancer induced by diethylnitrosamine in rats.

BACKGROUND: It is generally accepted that spleen plays a complex role in the tumor immunity, which would change in the different periods of cancer. In this study, we investigated the changes in the function of splenic macrophage (Mphi) in different stages of liver cancer induced by diethylnitrosamine (DEN) in rats. The aim was to support the characteristics of "two-way" and "phase" of spleen in tumor immunity. METHODS: The model of pulmonary metastasis of liver cancer was established in forty male SD rats by DEN. In the 8th, 13th and 16th week, 10 rats were randomly chosen and sacrificed, and divided into cirrhosis, liver cancer and pulmonary metastasis groups depending on the pathological result, respectively. The other 10 rats were taken as control group. The Mphi was isolated by anchoring cultivation. The changes in ultrastructure, phagocytosis, cytokine secretion, antigen processing and presenting, and viability of splenic Mphi were detected by transmission electron microscopy, Vybrant(TM) Phagocytosis Assay, DQ(TM) Ovalbumin, and rat TNF-alpha ELISpot kits. RESULTS: Under the electron microscope, the Mphi in the control group had some pseudopodium-like prominences, and mitochondria, ribosome, rough endoplasmic reticulum, lysosome can be found in the cytoplasm, and phagocytized RBC. In the liver cirrhosis and liver cancer group, Mphi had more prominences, meanwhile much more mitochondria, ribosome, rough endoplasmic reticulum, lysosome can be found in the cytoplasm, especially in the liver cancer group. In the pulmonary metastasis group, the Mphi was swelling, with few organelle. As compared to the control group, the function of splenic Mphi increased in cirrhosis and cancer groups, but decreased in metastasis group (phagocytosis rate: (84.7 +/- 1.9)%, (89.5 +/- 3.1)%, and (36.0 +/- 2.6)% vs (75.6 +/- 1.7)%, P < 0.05, P < 0.01; viability: (1.53 +/- 0.15)%, (1. +/- 0.14)%, and (1.12 +/- 0.29)% vs (1.48 +/- 0.17)%, P < 0.05, P < 0.01; TNF-alpha secretion: (741.0 +/- 52.9)%, (1126.2 +/- 174.5)%, and (313.8 +/- 50.8)% vs (626.6 +/- 24.6)%, P < 0.05, P < 0.01; positive cell rate of antigen processing and presenting: (24.03 +/- 1.87)%, (27.95 +/- 2.63)%, and (10.46 +/- 2.16)% vs (16.45 +/- 1.86)%, P < 0.01). CONCLUSIONS: In the stage of cirrhosis and early cancer, the immune functions of splenic Mphi were reinforced. It may promote the non-specificity tumor immunity. On opposite, in the stage of pulmonary metastasis, the immune functions of splenic Mphi were impaired. It may lead to the decrease of tumor immunity.