Effect of Individualized Cardiac Rehabilitation on Cardiac Function, Time Consumption, and Quality of Life in Patients After CABG.

BACKGROUND: To investigate the effect of individualized cardiac rehabilitation (CR) on cardiac function, time consumption, and quality of life (QoL) in post-CABG patients. METHODS: Two different CR strategy: basic rehabilitation and individualized rehabilitation was designed. The patients were screened and randomized into the two groups: the basic rehabilitation group (BRG) and individualized rehabilitation group (IRG). Data, such as clinical characteristics, LVEF, 6MWD (6-min walk distance), BNP, LVEDD (left ventricular end diastolic dimension), SF-36 score, and time consumption were collected and recorded. RESULTS: There was no difference between the IRG and BRG patients in the clinical characteristics. The 6MWD and LVEF on post-op significantly were higher, while BNP and LVEDD significantly was lower in the IRG than in BRG. The time to first out-of-bed activity, ICU stay time, and post-op hospital stay time of the IRG in post-op was significantly shorter than BRG. The IRG patients scored significantly higher on the SF-36. CONCLUSION: Individualized CR is safe and can reduce the time consumption and improve the cardiac function and QoL of patients undergoing CABG.

Silencing lncRNA NEAT1 reduces nonalcoholic fatty liver fat deposition by regulating the miR-139-5p/c-Jun/SREBP-1c pathway.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) starts with the abnormal accumulation of lipids in the liver. Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) was reported to modulate hepatic metabolic homeostasis in NAFLD. However, little is known about the molecular mechanisms of NAFLD. MATERIALS AND METHODS: To establish a NAFLD cellular model, HepG2 cells and LO2 cells were treated with 1 mM free fatty acids (FFAs) for 24 h. NEAT1, miRNA (miR)-139-5p, c-Jun and sterol-regulatory element binding protein-1c (SREBP-1c) were evaluated using qPCR. The protein levels of c-Jun, SREBP1c, acetyl-CoA carboxylase (ACC) and fatty acid synthetase (FAS) were determined using western blotting. Moreover, Oil Red O staining was employed to assess lipid accumulation. In addition, a kit assay was performed to evaluate TG levels. Finally, the interactions among NEAT1, miR-139-5p, c-Jun and SREBP1c were identified by dual luciferase reporter gene assay. RESULTS: NEAT1, c-Jun and SREBP1c expression was markedly elevated, while miR-139-5p expression was reduced in the NAFLD cellular model. NEAT1 knockdown restrained lipid accumulation in the NAFLD cellular model by directly targeting miR-139-5p. Moreover, miR-139-5p overexpression suppressed lipid accumulation by directly suppressing c-Jun expression. In addition, c-Jun silencing suppressed lipid accumulation by directly targeting SREBP1c. Finally, miR-139-5p inhibition mitigated the inhibitory effect of sh-NEAT1 on lipid accumulation. CONCLUSION: NEAT1 aggravated FFA-induced lipid accumulation in hepatocytes by regulating the c-Jun/SREBP1c axis by sponging miR-139-5p, indicating the potential of NEAT1 as a promising therapeutic target for NAFLD.

Hyperactivated peripheral invariant natural killer T cells correlate with the progression of HBV-relative liver cirrhosis.

Invariant NKT (iNKT) cells express markers of both T and NK cells and may produce various cytokines to regulate liver immunity. However, the role of iNKT cells in the progression of HBV-relative liver cirrhosis (HBV-LC) is incompletely understood. Here, we investigated the impact of peripheral iNKT cells on a cohort of patients with HBV-LC. The frequency, number, activation status, apoptosis and proliferation ability of peripheral iNKT cells were detected with flow cytometry. The impact of peripheral iNKT cells on the proliferation of hepatocyte cell line (MIHA) and activation of hepatic stellate cell line (LX-2) was detected with flow cytometry and PCR. In HBV-LC patients, the frequency and absolute number of peripheral iNKT cells significantly reduced, but the expression levels of CD25, interleukin (IL)-4, IL-13 and interferon (IFN)-γ increased. No difference was observed in the proliferation and apoptosis of circulating iNKT cells between patients and healthy controls (HCs). CXCR6 (CD186), known to be closely associated with iNKT cells migration from the periphery to the liver, was highly expressed on peripheral iNKT cells in HBV-LC patients. Furthermore, peripheral iNKT cells had a profound impact on MIHA cell proliferation and LX-2 cell activation through IL-4 or IL-13. Our data suggest that in HBV-LC patients, highly activated peripheral iNKT cells may migrate to the liver and affect hepatocyte cell line (MIHA) proliferation and hepatic stellate cell line (LX-2) activation through the expression of type 2 cytokines, which may result in excessive healing and contributing to the progression of fibrosis toward cirrhosis in liver.

Anti-hypoxic effect of dihydroartemisinin on pulmonary artery endothelial cells.

BACKGROUND: Previous studies have found that dihydroartemisinin (DHA) has multiple functions such as anti-inflammatory, anti-tumor in addition to anti-malarial effects. Effect of DHA on monocrotaline-induced pulmonary hypertension in rats has been reported, while the specific mechanism is not known. METHOD: A hypoxic model was established with human pulmonary arterial endothelial cells (HPAECs) to investigate the possible mechanism of DHA. Effects of DHA on proliferation of HPAECs were evaluated by CCK-8 and EdU assay. Effects of DHA on cell oxidative stress, cell migration, angiogenesis, cell cycle and autophagy, as well as the possible underlying mechanism were also detected by using the established normoxia/hypoxia cell models. RESULTS: DHA significantly inhibited hypoxia induced increase of HPAECs proliferation in a dose dependent manner, migratory ability and angiogenic ability. DHA also significantly reversed hypoxia induced oxidative stress as a reduction of ROS and NO, and an increase of SOD. Autophagosomes, LC3B protein and apoptotic proteins were significantly increased in DHA treated hypoxic HPAECs. Autophagy inhibitor 3-Methyladenine diminishes the anti-hypoxia effects of DHA on cell proliferation, migration, and autophagy and apoptosis protein expression in HPAECs. CONCLUSION: DHA effectively inhibits hypoxia induced increase of cell proliferation, migration, and oxidative stress in HPAECs, and autophagy may be the underlying mechanism of DHA.

Extraction and detection of bisphenol A in human serum and urine by aptamer-functionalized magnetic nanoparticles.

A new type of magnetic nanoparticles (MNPs), as the absorbents of bisphenol A (BPA), was prepared by functionalization of Fe3O4@SiO2 with BPA-specific aptamer in this work. ssDNA aptamer was immobilized on the Fe3O4@SiO2 surface through biotin-avidin interactions, playing a role of the specific probe for BPA. The resultant materials (Apt-MNPs) exhibited outstanding magnetic responsibility and can be separated efficiently by the magnetic field. Experimental results also showed that Apt-MNPs had large adsorption capacity and high competitive selectivity for the targeted compound BPA. Furthermore, Apt-MNPs were adopted as the specific absorbents to extract and enrich BPA from human serum and urine samples. Therefore, an efficient detection method of BPA was developed in combination with high-performance liquid chromatography (HPLC). The linearity of the method was over a range of 5-10,000 ng mL-1 with a correlation coefficient of 0.99997, and the limit of detections (LODs) for serum and urine were 2.0 and 1.0 ng mL-1, respectively. The recoveries of BPA in the spiked human serum and urine samples were 90.8 ± 7.3% (RSD) and 92.3 ± 1.5%, respectively. Our results demonstrated that Apt-MNPs were high-performance adsorbents for extracting and enriching BPA, resulting in fast and efficient detection of BPA in serum and urine samples. Graphical abstract Aptamer-MNPs were effective for BPA separation from serum and urine.

Hospitalization of elderly diabetic patients: characteristics, reasons for admission, and gender differences.

BACKGROUND: Understanding the differences in characteristics, gender, and common causes for admission in hospitalized elderly diabetic patients provides a theoretical basis for their successful management. This study explored the reasons and gender differences in hospitalizations of elderly patients with diabetes mellitus. METHODS: Patients aged ≥60 years who had received a diagnosis of diabetes by the time of discharge, from 1 January 2011 to 1 January 2014, were retrospectively enrolled. Hospitalization data of the patients were collected, and reasons for hospitalization were analyzed based on chief complaints and principle diagnosis. RESULTS: The most frequent reasons stated for admission were related to the chronic complications of diabetes (42.1 %), seconded by hyperglycemia (26.4 %) and infection (15.7 %). Ketonuria, ketonemia, or diabetic ketoacidosis was more commonly seen in women than men, whereas diabetic nephropathy and neoplasms were more frequently found in men than women. Regarding infection as a cause of hospitalization, the 4 main types were respiratory tract (44.5 %), urinary tract (20.3 %), gastrointestinal (14.8 %), and skin and soft tissue (10.9 %). Respiratory tract infection was significantly more common in men (61.4 %) than women (31 %, P = 0.001), whereas urinary tract infection was more frequent in women (29.6 %) than men (8.8 %, P = 0.004). CONCLUSION: The most frequent reasons for hospital admission in elderly diabetic patients were chronic complications of diabetes, hyperglycemia, and infection. Men and women differed in reasons for hospital admission.

DNAzyme-based sensing probe protected by DNA tetrahedron from nuclease degradation for the detection of lead ions.

Lead poisoning endangers soil, plants and human health due to its toxic effect. It is urgent to develop ideal tool for the in vivo detection of Pb2+.In this study, tetrahedron-based Pb2+-sensitive DNAzyme sensor (TPS) is constructed by taking advantages of a classic Pb2+-dependent GR-5 DNAzyme and DNA tetrahedral structure, where the cleavage substrate and DNAzyme are modified with fluorophore FAM and quencher BHQ-1, respectively. DNA tetrahedron is arranged at the terminus of substrate/DNAzyme duplex to offer the protective shield against the nuclease attack. In the absence of Pb2+, FAM and BHQ-1 are kept close and FAM fluorescence is efficiently quenched. However, in the presence of Pb2+ cofactor, the DNAzyme exhibits the catalytic activity and cleaves the substrate strands, spatially separating the FAM away from BHQ-1 and releasing fluorescence. Utilizing the sensing probe, the Pb2+ can be quantitatively detected down to 1 nM without the interference from nontarget metal ions. Even if incubating in the human serum solution for 12 h, no substantial nuclease degradation is detected. In different complex biological milieu, the TPS can preserve the 85% of fluorescence signal, indicating that the developed TPS is a promising tool for the future application in the in vivo detection of Pb2+.

lncRNA NEAT1 regulates fibrosis and inflammatory response induced by nonalcoholic fatty liver by regulating miR-506/GLI3.

As one of the most common liver disorders worldwide, nonalcoholic fatty liver disease (NAFLD) begins with the abnormal accumulation of triglyceride (TG) in the liver and can lead to inflammation and fibrosis. Long noncoding RNA (lncRNA) NEAT1 was reported to promote NAFLD progress. However, its molecular mechanism in NAFLD was not fully clear. In vitro cellular model of NAFLD was established with BRL3A cell treated by free fatty acid (FFA). Cell Counting Kit-8 (CCK-8) assay was carried out to assess cell proliferation. The expression of mRNA and protein of inflammation and fibrosis in BRL3A cell was detected by qRT-PCR and Western blot. Bioinformatics and dual-luciferase reporter assays were used to predict and validate the interaction between NEAT1 and miR-506 as well as GLI3 and miR-506. NEAT1 was upregulated while miR-506 was downregulated in the progression of NAFLD. Meanwhile, NEAT1 and miR-506 were proved to regulate fibrosis, inflammatory response, and lipid metabolism. Knockdown of NEAT1 inhibited GLI3 expression and promoted miR-506 expression, Overexpression of miR-506 inhibited NEAT1 and GLI3 expression. Moreover, dual-luciferase reporter assays proved that miR-506 could bind to NEAT1 and GLI3, whereas NEAT1 could sponge miR-506 to regulate GLI3 expression. lncRNA NEAT1 could regulate fibrosis, inflammatory response, and lipid metabolism via the miR-506/GLI3 axis as a ceRNA, which is a novel mechanistic role in the regulation of NAFLD. These results provide a new potential treatment target for NAFLD.

Effect of the hepatitis B virus S­ecdCD40L vaccine therapy in HBV transgenic mice: A vaccine­induced activation of antigen presenting dendritic cells.

The classical hepatitis B virus (HBV) DNA vaccination plasmid only encodes for a single viral antigen, either the S or the PreS2/S antigen. Many strategies have been employed to improve the effect of these DNA vaccines. Our previous study identified that the fusion gene, HBV S­ecd cluster of differentiation 40 ligand (CD40L), may promote the activation of dendritic cells (DCs) and enhance their function in vitro. In the current study, the effect of HBV S­ecdCD40L vaccine therapy on liver DCs was investigated, and its therapeutic potential in HBV transgenic (HBV­Tg) mice was evaluated. The eukaryotic expression plasmid, pcDNA3.1­S­ecdCD40L, was constructed by inserting the HBV S gene and mouse CD40L gene into the vector, pcDNA3.1 (+). HBV­Tg mice were immunized with pcDNA3.1­S­ecdCD40L, pcDNA3.1­S, pcDNA3.1 or PBS. Following this, immunophenotyping, cytokine production and T­cell activation were analyzed in the CD11c­enriched DC population obtained from the liver. Vaccine efficacy was further assessed by the detection of serological and biochemical parameters. When comparing with other control groups, DCs from HBV­Tg mice immunized with pcDNA3.1­S­ecdCD40L exhibited increased expression of immunologically important cell molecules (CD86 and major histocompatibility complex class II), pro­inflammatory cytokines (interleukin­12), and enhanced capacity to promote allogeneic T­cell proliferation. Furthermore, the HBV S­ecdCD40L vaccine resulted in a significant inhibition of HBV DNA replication and downregulation of the hepatitis B virus surface antigen (HBsAg) in HBV­Tg mice, without obvious liver injury. In conclusion, the HBV S­ecdCD40L vaccine may be a feasible strategy for chronic HBV immunotherapy via promoting DC activation and function.

Cell-specific expression of the analgesic-antitumor peptide coding sequence under the control of the human α-fetoprotein gene promoter and enhancer.

The aim of the present study was to construct a gene-modified hepatocellular carcinoma (HCC)-specific analgesic-antitumor peptide (AGAP) expression vector regulated by the α-fetoprotein (AFP) promoter and enhancer, in order to evaluate its effect. The AFP promoter is generally used in HCC-specific gene therapy strategies. However, this approach is limited by the weak activity of the AFP promoter. Linking the AFP enhancer and promoter has been shown to generate a stronger and more HCC-selective promoter. The AGAP DNA fragment was amplified from the total RNA of the Chinese scorpion, Buthus martensii Karsch. The fragment was subsequently cloned into the pAFP plasmid with the minimal essential DNA fragment, which included the AFP gene promoter and enhancer, to construct the recombinant plasmid, pAFP-AGAP. The plasmid was transfected into HepG2 cells and the mRNA expression levels of AGAP were detected by reverse transcription polymerase chain reaction (RT-PCR). In addition, Cell Counting Kit 8 (CCK-8) was used to analyze the cytotoxicity of plasmid transfection. The length, position and orientation of the inserted AGAP gene were all confirmed to be correct; thus, the recombinant vector was successfully constructed. Using RT-PCR and CCK-8 analysis, the mRNA expression levels of AGAP and the cytotoxicity in AFP-producing human HCC cells were determined. The AFP promoter and enhancer were found to specifically accelerate the expression of the target genes within the cells that were positive for AFP. Therefore, the method used in the present study was demonstrated to be a novel integration of traditional Chinese medicine with western medicine.