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Nisoldipine can effectively suppress pulmonary arterial smooth muscle cell proliferation and c-Fos expression. To identify the mechanism of the anti-inflammatory effects in monocrotaline-induced pulmonary arterial hypertension (PAH), focusing on the c-Fos/NLRP3/caspase-1 pathway. In a mice model of monocrotaline-induced PAH, miRNA-155 expression was increased. In an in vitro model, overexpression of miRNA-155 promoted inflammation and induced c-Fos, NLRP3, and caspase-1 protein expression. The inhibition of c-Fos reduced the effects of miRNA-155 on inflammation in an in vitro model of monocrotaline-induced PAH. The inhibition of NLRP3 reduced the effects of miRNA-155 on inflammation in an in vitro model of monocrotaline-induced PAH. miRNA-155 increased inflammation in monocrotaline-induced PAH through c-Fos/NLRP3/caspase-1.

Wild and cultivated Licorice ( Glycyrrhiza uralensis FISCH.) are the main source of licorice. In recent years, wild Glycyrrhiza plants have been seriously damaged and this has reduced the population. The cultivation of Licorice has been the best way to solve the problem of its shortage. The contents of glycyrrhizic acid greatly differs in licorices cultivated at different region of China. However, the contents of glycyrrhizic acid in cultivated licorice in china is lower than that of wild licorice. To produce the high quality cultivated licorices, researchers studied the factors affecting the glycyrrhizic acid produced in licorice. It was found that manganese (Mn) application improved the medicinal material yieldand quality especially the contents of the glycyrrhizic acid. In this paper, we investigated the effects of Mn on the accumulation of glycyrrhizic acid in medicinal materials based on the material ingredients distribution and also explored the mechanism. The influence of Mn on the relative contents of glycyrrhizic acid were significant except for day 30 while the influence is significant to the absolute contents all the time. The relative contents of glycyrrhizic acid increased while the contents of crude protein, crude fiber and total material ingredients decreased. The absolute contents of glycyrrhizic acid rose when crude protein contents increased. This implies that the contents of glycyrrhizic acid are in a close relationship with material ingredients. Mn application of appropriate concentration could stimulate the formation of primary metabolites, and then promote the secondary metabolism of G. uralensis which could lead to the formation and accumulation of glycyrrhizic acid in G. uralensis .

Objective: A sensitive HPLC-DAD detection method was established for the comparative analysis of the four active compounds (including baicalin, baicalein, wogonoside and wogonin) of Baikal Skullcap and its classical TCM prescriptions according to different clinical curative effects. And analyze the relationship between compatibility of medicines, content and clinical curative effect.

Objective. miRNA has gained attention as a therapeutic target in various malignancies. The proposal of this study was to investigate the biological functions of key miRNAs and target genes in cancers of the digestive tract which include esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colon adenocarcinoma (COAD), and rectal adenocarcinoma (READ). Materials and Methods. After screening differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) in four digestive cancers from The Cancer Genome Atlas (TCGA) database, the diagnostic value of above DEMIs was evaluated by receiver-operating characteristic (ROC) curve analysis. Then, corresponding DEMIs’ target genes were predicted by miRWalk 2.0. Intersection of predicted target genes and DEMs was taken as the target genes of DEMIs, and miRNA-mRNA regulatory networks between DEMIs and target genes were constructed. Meanwhile, the univariate Cox risk regression model was used to screen miRNAs with distinct prognostic value, and Kaplan–Meier analysis was used to determine their significance of prognosis. Furthermore, we performed bioinformatics methods including protein-protein interaction (PPI) networks, gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene group RIDA analysis by Gene-Cloud of Biotechnology Information (GCBI) to explore the function and molecular mechanisms of DEMIs and predicted target genes in tumor development. Results. Eventually, 3 DEMIs (miR-7-3, miR-328, and miR-323a) with significant prognostic value were obtained. In addition, 3 DEMIs (miR-490-3p, miR-133a-3p, and miR-552-3p) and 281 target genes were identified, and the 3 DEMIs showed high diagnostic value in READ and moderate diagnostic value in ESCA, GAC, and COAD. Also, the miRNA-mRNA regulatory network with 3 DEMIs and 281 overlapping genes was successfully established. Functional enrichment analysis showed that 281 overlapping genes were mainly related to regulation of cell proliferation, cell migration, and PI3K-Akt signaling pathway. Conclusion. The diagnostic value and prognostic value of significant DEMIs in cancers of the digestive tract were identified, which may provide a novel direction for treatment and prognosis improvement of cancers of the digestive tract.

Aim: The present study aimed to examine the correlation between high-sensitivity CRP to albumin ratio (CAR) and in-hospital and short-term major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). Materials & methods: We analyzed 652 consecutive patients who had been hospitalized for ACS. The MACEs were defined as cardiogenic shock, reinfarction, acute heart failure and all-cause death. Results: The incidence rate of MACEs was significantly higher in the high CAR (≥0.114) group than in the low CAR (

Physiological variation and adaptation of the long-term evolved rhizobia to alkaline environments where no host plant existence and the stability of their symbiotic properties when they are reinoculated to legume host remain unclear. A highly effective N2-fixing Rhizobium yanglingense strain CCBAU 01603 was used as the ancestral strain and was cultured continuously with/without addition of extra alkaline reagent (KOH) in laboratory conditions for approximately 500 generations. Total 60 evolved clones obtained were checked for their adaptation to higher alkaline pH level and inoculated to their host plant Caragana microphylla to evaluate their symbiotic efficiencies. Most of the evolved clones showed increased adaptation to higher alkaline pH but all of them decreased symbiotic efficiencies, resulting in the formation of irregular root nodules with lower nitrogenase activity, production of abnormal bacteroids, and accumulation more starch grains in uninfected nodule cells. Further demonstration of lower symbiotic efficiencies came from the down-regulated expression of genes related to nitrogen fixation in the bacteroids by transcriptome comparison. In addition, genes related to transporters and other diverse functions were up- or down-regulated in the evolved clones in free-living conditions (like yjiS gene) or in symbiotic situations, demonstrating the significant variations in cellular physiology and symbiosis. Our study revealed that the enhancement of alkaline adaptation but loss of symbiotic efficiencies of the evolved clones had happened during the long-term evolution in alkaline environments where no selective pressures from host plant, offering new insight into the molecular mechanism and direction of rhizobial evolution in nature.

The aim of this study is to evaluate if low prealbumin levels on admission predict subsequent adverse cardiac events in patients hospitalized with acute coronary syndrome (ACS). We designed a cohort study and enrolled 610 consecutive patients with ACS from whom venous blood for serum prealbumin measurement was drawn immediately upon hospital admission. Patients were classified in two groups according to prealbumin level: “normal” prealbumin levels (≥17 mg/dL, n=413) and “low” prealbumin (

Our aim was to investigate the role of interleukin-6 (IL-6) in myocardial regeneration from mice after cardiac injury. The newborn mice were divided into the following 4 groups (16 in each group): sham group, model group, IL-6-/- group (IL-6 knockout) and IL-6 group (IL-6 overexpression). Electrocardiography was performed on all mice and found higher LVEDD, LVESD and IVST and lower LVEF and LVFS in the IL-6 group compared with the sham group. Using HE staining, severe myocardial injury combined with infarction and fibrosis were observed in the IL-6-/- group, while the damaged myocardial tissue was repaired to some extent in the IL-6 group. The expression of IL-6 in the IL-6 group were significantly up-regulated. BrdU immunofluorescence found that the IL-6-/- group had the least number of BrdU positive cells, while the IL-6 group had more BrdU positive cells than the model group and the IL-6-/- group. Expressions of IL-6, cyclinD1 and Bcl-2 in the IL-6 group were up-regulated compared with other groups. In conclusion, IL-6 overexpression could enhance cardiomyocyte proliferation and relevant protein expression in mice myocardium, thus promoting cardiac regeneration.

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75–100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8–2.5 and 1.5–2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

To evaluate the therapeutic effects of prostaglandin E(1) (PGE(1)) on residual pulmonary arterial hypertension (PAH) after corrective surgery for congenital heart disease.Thirty-one patients with postoperational PAH were randomly divided into control group (n = 15) and PGE(1) group (n = 16, 6 courses of intravenous PGE(1) plus conventional therapy). Mean pulmonary arterial pressure (MPAP), right ventricular ejection fraction (RVEF), and left ventricular ejection fraction (LVEF) were measured by echocardiography before and 3, 6, and 12 months after the treatment. Arterial oxygen pressure (Pao (2)) was monitored.In both groups, MPAP decreased and RVEF, LVEF, and Pao (2) increased at 6 and 12 months following surgery. In the PGE(1) group, the MPAP (32.2 ± 5.2 vs 40.2 ± 5.1 mm Hg; P = .008) was lower and RVEF (66.6% ± 6.5% vs 54.9% ± 2.1%; P = .019), LVEF (65.9% ± 3.9% vs 53.5% ± 5.1%; P = .031), and Pao (2) (94.3% ± 11.2% vs 93.1% ± 11.3%; P = .009) was higher than in the control group 12 months after the surgery. Four patients (26.7%) in the control group died of pulmonary hypertension crisis, but there was no death in the PGE(1) group (P = .029). Cumulative survival rate in the control group were 86.7%, 80%, 73.3%, and 73.3% at 1, 2, 3, and 5 years, respectively.Intravenous PGE(1) therapy after corrective surgery for congenital heart disease was associated with a reduction in mean pulmonary arterial pressure and a lower risk of death.

Introduction This study was designed to evaluate safety and efficacy of combined low dose aspirin and warfarin therapy following mechanical heart valve replacement. Methods A total of 1 496 patients (686 males, mean age 35 ± 8.5 years) undergoing mechanical heart valvular replacement were randomly divided into study (warfarin plus 75–100 mg aspirin) or control (warfarin only) group. International normalized ratio (INR) and prothrombin time was maintained at 1.8-2.5 and 1.5-2.0 times of the normal value, respectively. Thromboembolic events and major bleedings were registered during follow up. Results Patients were followed up for 24 ± 9 months. The average dose of warfarin in the study and control group was 2.92 ± 0.87 mg and 2.89 ± 0.79 mg, respectively (p > 0.05). The overall thromboembolic events in study group were lower than in control group (2.1% vs. 3.6%, p = 0.044). No statistically significant differences were found in hemorrhage events (3.5% vs. 3.7%, p > 0.05) or mortality (0.3% vs 0.4%, p > 0.05) between the two groups. Conclusions Following mechanical valve replacement, combined low dose aspirin and warfarin therapy was associated with a greater reduction in thromboembolism events than warfarin therapy alone. This combined treatment was not associated with an increase in the rate of major bleeding or mortality.

A full-length cDNA sequence of xyloglucan endotransglycosylase gene (XET), abundantly expressed in the cambium of Anthocephalus chinensis was cloned by conserved PCR, rapid-amplification of cDNA ends and by chromosome walking. Analytical results of the DNA sequence show that a 912 bp complete open reading frame (ORF) encoded a 303-amino acid protein was in the 1205 bp full cDNA sequence. The deduced amino acid sequence of AcXET, which contained the conserved specific EIDFE catalytic site sequence to XETs was homologous to the other known XET proteins. In order to study the gene function of AcXET and obtain transgenic plants, a plant expression vector pBIAcXET was constructed by recombinating the AcXET fragment from the cloning vector pMD19AcXET and the binary vector pBI121 between the XbaI and SmaI sites. The fragment of AcXET gene was inserted between the CaMV 35S promotor and the coding region of the GUS gene in pBI121. The identification results show that the plant expression binary vector pBIAcXET was constructed successfully. These results lay the foundation for studying the molecular mechanism of AcXET gene during wood formation.

The transplants of one-year-old Glycyrrhiza uralensis Fisch. were subjected to five concentrations of MnSO4-H2O (0, 1.81, 18.1, 36.2 and 54.3 mg·L(-1)) culturing in vermiculite. qRT-PCR and HPLC were respectively used to measure the relative expression of SQS1 gene and the content of glycyrrhizic acid of G. uralensis in different concentrations of MnSO4·H2O. This is to explore discuss the effects of the expression of SQS1 gene and the accumulation of glycyrrhizic acid by Mn treatment. The results showed both the expression of SQS1 gene and the content of glycyrrhzic acid of G. uralensis tended to rise after the fall of the first with the increase of concentration of Mn treatment. And they were of very significant positive correlation (P0.01, r=0.737). Relative expression of SQS1 gene reached the highest 7.90 under 18.1 mg·L(-1) MnSO4·H2O treatment. It was very significantly different between 18.1 mg·L(-1) concentration of MnSO4·H2O treatment and CK (0 mg·L(-1)), 1.81, 36.2 and 54.3 mg·L(-1) (P0.01), and 1.75, 1.37, 1.37, 2.33 times respectively. The content of glycyrrhizic acid reached the highest under 1.81 and 18.1 mg·L(-1) MnSO4·H2O treatment, and there were not significant difference (P0.05). It was very significantly different between them and other concentrations of MnSO4·H2O treatment (P0.01). This study suggests the appropriate concentration of Mn treatment could certain promote the expression of SQS1 gene and the accumulation of glycyrrhizic acid of G. uralensis.

Background: This study was designed to investigate the effect of captopril on systolic pulmonary arterial pressure (PAP) and circulating endothelin-1 (ET-1) following surgical repair of tetralogy of Fallot (TOF). Methods and Results: Seventy-six consecutive patients were divided into captopril and control groups following successful repair of TOF. The captopril group was treated with oral captopril (0.2 mg/kg/day) for 12 months. Venous blood was taken before and after the surgery for the analysis of ET-1. Systolic PAP and ventricular function were assessed by Doppler echocardiography. In the control group, there was an increase in ET-1 and systolic PAP following the surgery (p < 0.05). In the captopril group, there was no significant increase in the systolic PAP and ET-1 during the 12-month follow-up. The PAP and ET-1 values in the captopril group were lower than those in the control group following the surgery (p < 0.05). Conclusions: Systolic PAP is elevated following the complete surgical repair of TOF. Increased circulating ET-1 may be responsible for the elevation of PAP. Captopril treatment prevents postsurgical increases in systolic PAP and circulating ET-1.

Background Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboses. To address the association of genetic factors and warfarin dosage for ethnic Han Chinese, we genotyped six candidate genes involved in the warfarin interactive pathway with focus on SNPs with reported association with warfarin dose. Methods We recruited a study population consisted of 318 patients receiving warfarin treatment and 995 healthy controls. PCR and direct sequencing were used to identify the sequence polymorphisms. Results In our study population, SNP rs1799853 of CYP2C9 , rs1687390 of ORM1–2 , and rs2069919 of PROC showed no variation. SNPs rs12714145 of GGCX and rs1799809 of PROC showed no significant correlation with warfarin dose. The associations of SNPs rs9934438 and rs9923231 of VKORC1 , the ⁎3 (rs1057910) and C − 65 (rs9332127) alleles of CYP2C9 , and SNP rs4653436 of EPHXI with the dose of warfarin were significant. Conclusion A multiple regression model based on the genetic polymorphisms of VKORC1 , CYP2C9 , EPHX1 and the non-genetic factors of age and body weight can explain 40.2% of the variance in warfarin dose in Han Chinese patients. Translation of this knowledge into clinical guidelines for warfarin prescription may improve the safety and efficacy of warfarin treatment among Han Chinese.