Systematic exploration of the potential material basis and molecular mechanism of the Mongolian medicine Nutmeg-5 in improving cardiac remodeling after myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Nutmeg-5, which consists of Myristica fragrans Houtt., Aucklandia lappa Decne., Inula helenium L., Fructus Choerospondiatis and Piper longum L., is an ancient and classic formula in traditional Mongolian medicine that is widely used in the treatment of ischemic heart disease. However, its material basis and pharmacological mechanisms remain to be fully elucidated. AIM OF THE STUDY: The aim of this study was to explore the potential material basis and molecular mechanism of Nutmeg-5 in improving cardiac remodeling after myocardial infarction (MI). MATERIALS AND METHODS: The constituents of Nutmeg-5 absorbed into the blood were identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). A mouse MI model was induced in male Kunming mice by permanent ligation of the left anterior descending coronary artery (LDA) ligation. Echocardiography was performed to assess cardiac function. The protective effect of Nutmeg-5 and compound Danshen dripping pills as positive control medicine on post-MI cardiac remodeling was evaluated by tissue histology and determination of the serum protein levels of biomarkers of myocardial injury. RNA sequencing analysis of mouse left ventricle tissue was performed to explore the molecular mechanism of Nutmeg-5 in cardiac remodeling after MI. RESULTS: A total of 27 constituents absorbed into blood were identified in rat plasma following gavage administration of Nutmeg-5 (0.54 g/kg) for 1 h. We found that ventricular remodeling after MI was significantly improved after Nutmeg-5 treatment in mice, which was demonstrated by decreased mortality, better cardiac function, decreased heart weight to body weight and heart weight to tibia length ratios, and attenuated cardiac fibrosis and myocardial injury. RNA sequencing revealed that the protective effect of Nutmeg-5 on cardiac remodeling after MI was associated with improved heart metabolism. Further study found that Nutmeg-5 treatment could preserve the ultrastructure of mitochondria and upregulate gene expression related to mitochondrial function and structure. HIF-1α (hypoxia inducible factor 1, alpha subunit) expression was significantly upregulated in the hearts of MI mice and significantly suppressed in the hearts of Nutmeg-5-treated mice. In addition, Nutmeg-5 treatment significantly activated the peroxisome proliferator-activated receptor alpha signaling pathway, which was inhibited in the hearts of MI mice. CONCLUSIONS: Nutmeg-5 attenuates cardiac remodeling after MI by improving heart metabolism and preserving mitochondrial dysfunction by inhibiting HIF-1α expression in the mouse heart after MI.

Circulating IgGs in Type 2 Diabetes with Atrial Fibrillation Induce IP3-Mediated Calcium Elevation in Cardiomyocytes.

Higher risk of cardiac arrhythmias including atrial fibrillation (AF) associates with type 2 diabetes mellitus (T2DM) with the underlying mechanism largely unknown. The present study reported a subset of circulating immunoglobulin G autoantibodies (IgGs) from patients with T2DM with AF (T2DM/AF)-induced intracellular calcium elevation in both human induced pluripotent stem cell (iPSC)-derived and mouse atrial cardiomyocytes, whereas (identical concentrations of) IgGs from patients with T2DM without AF could not. The IgG-evoked intracellular calcium elevation was insensitive to verapamil, mibefradil, or BTP-2, indicating calcium source from neither voltage-gated calcium channels nor store-operated calcium entry. On the other hand, pharmacological antagonism or genetic knockdown of inositol triphosphate (IP3) receptor significantly decreased T2DM/AF IgG-induced intracellular calcium elevation. Furthermore, pharmacological blockage of G protein-coupled receptor (GPCR), heterotrimeric G protein or phospholipase C dampened IgG-induced intracellular calcium elevation. Taken together, circulating IgGs from patients with T2DM/AF stimulated arrhythmogenic intracellular calcium elevation through IP3 pathway in atrial cardiomyocytes.

Identification lncRNA LOC102551149/miR-23a-5p pathway in hepatic fibrosis.

BACKGROUND: Hepatic fibrosis is a worldwide incurable disease; due to the complex and unclear mechanism, there lack the effective therapeutic targets. However, the mechanism of miR-23a-5p underling this pathological process is largely not clear. The purpose of this study was to investigate the role of miR-23a-5p in hepatic fibrosis and HSC activation. METHODS: The content of miR-23a-5p in hepatic fibrosis induced by N-nitrosodimethylamine (NDMA) and HSC activation induced by platelet-derived growth factor (PDGF) was detected by qRT-PCR. H&E staining, Masson staining and Shear wave electrography (SWE) were used to detect the degree of hepatic fibrosis. Immunohistochemistry staining, qRT-PCR and Western blot detect the related markers of liver fibrosis or HSC activation, as well as the related pathway genes and proteins. Dual-luciferase reporter system verifies the interaction between miR-23a-5p with PTEN or miR-23a-5p with lncRNA LOC102551149 in HSC-T6. siRNA and miRNA mimic transfer to HSC-T6 to detect the function of lncRNA LOC102551149 and miR-23a-5p on HSC activation. RESULTS: After hepatic fibrosis and HSC activation happened, the expression of miR-23a-5p was up-regulated, whereas anti-miR-23a-5p can alleviate hepatic fibrosis and HSC activation. Further research shows miR-23a-5p can target PTEN and degrade it, causing activation of PI3K/Akt/mTOR/Snail pathway. lncRNA LOC102551149 can be used as a competition endogenous RNA (ceRNA) targeting miR-23a-5p through base pairing, and siRNA LOC102551149 or exogenous miR-23a-5p can induce HSC activation through PI3K/Akt/mTOR/Snail pathway. CONCLUSION: We demonstrate mechanism pathway of miR-23a-5p on hepatic fibrosis and HSC activation, which may develop a therapeutic target for hepatic fibrosis.

[Study on protective effect of vanillic acid from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology screen].

To identify and verify the active ingredients from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology and heart RNA-sequencing data. The monomers of A. membranaceus and their intervention target database were established by using network pharmacology. The genes associated to cardiac remodeling were then screened by analyzing cardiac RNA-sequencing data. An overlap between genes related to cardiac remodeling and targets of ingredients form A. membranaceus was collected to obtain monomers with protective effect on hypertensive cardiac remodeling. Angiotensin Ⅱ(AngⅡ)-induced mouse cardiac remodeling model was used to validate the protective effect of active ingredients from A. membranaceus on hypertensive cardiac remodeling. Finally, a total of 81 monomers and 1 197 targets were enrolled in our database. Mouse RNA-sequencing data showed that 983 genes were significantly up-regulated and 465 genes were down-regulation in myocardial tissues of the cardiac remodeling mice as compared with blank group mice, respectively. Ninety-two genes were found via overlapping between genes related to cardiac remodeling and targets, involving 59 monomers from A. membranaceus. Further research found that vanillic acid(VA) could intervene 27 genes associated with hypertensive cardiac remodeling, ranking top 1. Meanwhile, VA could significantly inhibit AngⅡ-induced increase in ratio of heart weight to body weight and heart weight to tibial length, ANP and BNP mRNA levels in myocardial tissues, myocardial tissue damage, cardiac fibrosis level and cardiac hypertrophy level in vivo. Those results showed that network pharmacology screen-based VA has protective effect on AngⅡ-induced cardiac remodeling.

Astragaloside IV reduces cardiomyocyte apoptosis in a murine model of coxsackievirus B3-induced viral myocarditis.

Apoptosis plays a crucial role in regulating cardiomyopathy and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that Astragaloside IV (AST-IV) from Astragalus membranaceus could inhibit apoptosis under a variety of pathological conditions in vivo or in vitro. However, the functional roles of AST-IV in CVB3-induced VM still remain unknown. Here, we found that AST-IV significantly enhanced survival for CVB3-induced mice. AST-IV protected the mice against CVB3-induced virus myocarditis characterized by the increased body weight, decreased serum level of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), supressed expression of Ifn-γ, Il-6 in heart, enhanced systolic and diastolic function of left ventricle. At the pathological level, AST-IV ameliorated the mice against CVB3-induced myocardial damage and myocardial fibrosis. In vitro, the results from flow cytometry showed that AST-IV significantly suppressed CVB3-induced cardiomyocytes apoptosis, which also were verified in vivo. Moreover, an increased expression of pro-apoptotic genes including FAS, FASL, cleaved caspase-8 and cleaved caspase-3 was found in CVB3-induced cardiomyocytes, while those was inhibited in cardiomyocytes treated with AST-IV. Taken together, the data suggest that AST-IV protected against CVB3-induced myocardial damage and fibrosis, which may partly attribute to supress activation of FAS/FASL signaling pathway.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin in patients with cancer: a systematic review and meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) are still debated in the treatment of patients with cancer, and the optimal duration of therapy remains uncertain. Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus LMWH in treating patients with cancer from January 1980 to October 2018. The primary efficacy and safety endpoints were recurrent venous thromboembolism (VTE) and major bleeding. Our study included two randomized controlled trials (RCTs) and nine observational studies, together comprising 4509 patients with cancer. The pooled estimates indicated that DOACs led to a modest reduction recurrent VTE in the RCTs [RR: 0.63, 95% confidence interval (CI), 0.42-0.96, P = 0.03] and in the observational studies (RR: 0.74, 95% CI, 0.58-0.93, P = 0.011), without increasing the risk of major bleeding for observational studies (P = 0.805), but increased for RCTs (P = 0.017). The same trends were observed in the rivaroxaban subgroup. Moreover, subgroup analyses according to the treatment duration indicated that DOACs significantly reduced the incidence of recurrent VTE (P = 0.006 at 6 months; P < 0.001 at 12 months) without significant differences in major bleeding compared with LMWH at 6 or 12 months. Patients with cancer who received DOACs exhibited a significant reduction in recurrent VTE with no increased risk of major bleeding compared with LMWH. DOACs may be an alternative choice for long-term anticoagulant therapy in patients with cancer.

lncRNA GAS5 restrains CCl4-induced hepatic fibrosis by targeting miR-23a through the PTEN/PI3K/Akt signaling pathway.

Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5), microRNA-23a (miR-23a), and phosphatase and tensin homolog (PTEN) play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a, and PTEN in the pathological process of hepatic fibrosis and hepatic stellate cell (HSC) activation. We used carbon tetrachloride (CCl4) intraperitoneal injections to establish a rat hepatic fibrosis model and exogenous transforming growth factor-ß1 to establish an HSC activation model. Quantitative RT-PCR, Western blot, dual-luciferase reporter system, and RNA pull-down assays were used to investigate which microRNAs and lncRNAs participate in the process of hepatic fibrosis and HSC activation. miR-23a expression increased significantly in hepatic fibrosis tissues and activated HSCs. miR-23a interaction with and degradation of PTEN further influenced the downstream signaling pathway phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail (PI3K/Akt/mTOR/Snail), causing E-cadherin expression levels to decrease and α-smooth muscle actin and collagen I expression levels to increase. lncRNA GAS5 can be used as a sponge platform for miR-23a to decrease miR-23a expression levels competitively. We revealed the role of the lncRNA GAS5/miR-23a/PTEN/PI3K/Akt/mTOR/Snail signaling pathway in hepatic fibrosis, providing molecular targets for the treatment of hepatic fibrosis. NEW & NOTEWORTHY This is the first study revealing that microRNA-23a (miR-23a) promotes hepatic fibrosis through the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail signaling pathway, and long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) can act as a sponge platform for miR-23a. Therefore, lncRNA GAS5/miR-23a may bring molecular targets for hepatic fibrosis therapy.

Electrical Stimulation Enhances Cardiac Differentiation of Human Induced Pluripotent Stem Cells for Myocardial Infarction Therapy.

AIMS: Electrical stimulation (EleS) can promote cardiac differentiation, but the underlying mechanism is not well known. This study investigated the effect of EleS on cardiomyocyte (CM) differentiation of human induced pluripotent stem cells (hiPSCs) and evaluated the therapeutic effects for the treatment of myocardial infarction (MI). RESULTS: Cardiac differentiation of hiPSCs was induced with EleS after embryoid body formation. Spontaneously beating hiPSCs were observed as early at 2 days when treated with EleS compared with control treatment. The cardiac differentiation efficiency of hiPSCs was significantly enhanced by EleS. In addition, the functional maturation of hiPSC-CMs under EleS was confirmed by calcium indicators, intracellular Ca2+ levels, and expression of structural genes. Mechanistically, EleS mediated cardiac differentiation of hiPSCs through activation of Ca2+/PKC/ERK pathways, as revealed by RNA sequencing, quantitative polymerase chain reaction, and Western blotting. After transplantation in immunodeficient MI mice, EleS-preconditioned hiPSC-derived cells significantly improved cardiac function and attenuated expansion of infarct size. The preconditioned hiPSC-derived CMs were functionally integrated with the host heart. INNOVATION: We show EleS as an efficacious time-saving approach for CM generation. The global RNA profiling shows that EleS can accelerate cardiac differentiation of hiPSCs through activation of multiple pathways. The cardiac-mimetic electrical signals will provide a novel approach to generate functional CMs and facilitate cardiac tissue engineering for successful heart regeneration. CONCLUSION: EleS can enhance efficiency of cardiac differentiation in hiPSCs and promote CM maturation. The EleS-preconditioned CMs emerge as a promising approach for clinical application in MI treatment. Antioxid. Redox Signal. 28, 371-384.

Immunogenicity of varicella zoster virus glycoprotein E DNA vaccine.

In the present study a eukaryotic expression vector of varicella zoster virus (VZV) glycoprotein E (gE) was constructed and enabled to express in COS7 cells. Furthermore, a specific immune response against the VZV gE eukaryotic expression plasmid was induced in BALB/c mice. The VZV gE gene was amplified using polymerase chain reaction (PCR) and cloned into a eukaryotic expression vector, pcDNA3.1. The recombinant vector was subsequently transfected into COS7 cells using a liposome transfection reagent. The recombinant protein was instantaneously expressed by the transfected cells, as detected by immunohistochemistry, and the recombinant pcDNA-VZV gE plasmid was subsequently used to immunize mice. Tissue expression levels were analyzed by reverse transcription-PCR. In addition, the levels of serum antibodies and spleen lymphocyte proliferation activity were investigated. The amplified target gene included the full-length gE gene (~2.7 kb), and the recombinant expression vector induced gE expression in COS7 cells. In addition, the expression plasmid induced sustained expression in vivo following immunization of mice. Furthermore, the plasmid was capable of inducing specific antibody production and effectively stimulating T cell proliferation. Effective humoral and cellular immunity was triggered in the mice immunized with the VZV gE eukaryotic expression vector. The results of the present study laid the foundation for future research into a VZV DNA vaccine.

Apoptosis-inducing effects of lentinan on the proliferation of human bladder cancer T24 cells.

The aim of this study was to explore the effects of lentinan on the proliferation of human bladder cancer T24 cells and the mechanism regarding the inhibition of cell growth. When gene regulation technique was used to build pcDNA3-TRPM8 expression plasmid, TRPM8 channel activator-lentinan was used for intervention to observe the proliferation of T24 cells. Flow cytometry cell screening method was used to observe the cell ratio of each cell cycle of T24 cells and the ratio of apoptotic and dying cells under the intervention of different concentrations of lentinan using PI single-staining and Annexin V-FITC/PI double-staining. JC-1 and DCFH-DA fluorescence probes were used to observe the influence of different concentrations of lentinan on the mitochondrial membrane potential of T24 cells and intracellular reactive oxygen species (ROS) by confocal microscope. pcDNA-TRPM8 plasmid was successfully constructed, and lentinan could inhibit the growth of T24 cells in a dose-dependent pattern. Lentinan played its biological effect through TRPM8 channel to further inhibit the growth of T24 cells, reduced the mitochondrial membrane potential of bladder cancer T24 cell line, and increased the generation of ROS in human bladder cancer T24 cell line. Lentinan led to mitochondrial depolarization or activation of non-mitochondrial pathway to induce intracellular ROS generation, thus eventually inducing T24 cell death and growth inhibition.

Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction.

Background and Objective. Exosomes secreted from mesenchymal stem cells (MSC) have demonstrated cardioprotective effects. This study examined the role of exosomes derived from MSC overexpressing CXCR4 for recovery of cardiac functions after myocardial infarction (MI). Methods. In vitro, exosomes from MSC transduced with lentiviral CXCR4 (Exo(CR4)) encoding a silencing sequence or null vector were isolated and characterized by transmission electron microscopy and dynamic light scattering. Gene expression was then analyzed by qPCR and Western blotting. Cytoprotective effects on cardiomyocytes were evaluated and effects of exosomes on angiogenesis analyzed. In vivo, an exosome-pretreated MSC-sheet was implanted into a region of scarred myocardium in a rat MI model. Angiogenesis, infarct size, and cardiac functions were then analyzed. Results. In vitro, Exo(CR4) significantly upregulated IGF-1α and pAkt levels and downregulated active caspase 3 level in cardiomyocytes. Exo(CR4) also enhanced VEGF expression and vessel formation. However, effects of Exo(CR4) were abolished by an Akt inhibitor or CXCR4 knockdown. In vivo, Exo(CR4) treated MSC-sheet implantation promoted cardiac functional restoration by increasing angiogenesis, reducing infarct size, and improving cardiac remodeling. Conclusions. This study reveals a novel role of exosomes derived from MSC(CR4) and highlights a new mechanism of intercellular mediation of stem cells for MI treatment.

Significant reduction of antibiotic consumption and patients' costs after an action plan in China, 2010-2014.

INTRODUCTION: On July 1, 2011, the Chinese government launched a national Action Plan for antibiotic stewardship targeting antibiotic misuse in public hospitals. The aim of this study was to evaluate the impacts of the Action Plan in terms of frequency and intensity of antibiotic utilization and patients costs in public general hospitals. METHODS: Administrative pharmacy data from July 2010 to June 2014 were sampled from 65 public general hospitals and divided into three segments: (1) July 2010 to June 2011 as the preparation period; (2) July 2011 to June 2012 as the intervention period; and (3) July 2012 to June 2014 as the assessment period. The outcome measures included (1) antibiotic prescribing rates; (2) intensity of antibiotic consumption; (3) patients costs; and (4) duration of peri-operative antibiotic treatment in clean surgeries of thyroidectomy, breast, hernia, and orthopedic procedures. Longitudinal and cross-sectional analyses were conducted. RESULTS: Longitudinal analyses showed significant trend changes in the frequency and intensity of antibiotic consumption, the patients' costs on antibiotics, and the duration of antibiotic treatment received by surgical patients undergoing the 4 clean procedures during the intervention period. Cross-sectional analyses showed that the antibiotic prescribing rates were reduced to 35.3% and 12.9% in inpatient and outpatient settings, that the intensity of antibiotic consumption was reduced to 35.9 DDD/100 bed-days, that patients' costs on antibiotics were reduced significantly, and that the duration of peri-operative antibiotic treatment received by surgical patients undergoing the 4 types of clean procedures decreased to less than 24 hour during the assessment period. CONCLUSION: The Action Plan, as a combination of managerial and professional strategies, was effective in reducing the frequency and intensity of antibiotic consumption, patients' costs on antibiotics, and the duration of peri-operative antibiotic treatment in the 4 clean surgeries.

MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes.

Diabetes is the most common and complex metabolic disorder, and one of the most important health threats now. MicroRNAs (miRNAs) are a group of small non-coding RNAs that have been suggested to play a vital role in a variety of physiological processes, including glucose homeostasis. In this study, we investigated the role of miR-185 in diabetes. MiR-185 was significantly downregulated in diabetic patients and mice, and the low level was correlated to blood glucose concentration. Overexpression of miR-185 enhanced insulin secretion of pancreatic ß-cells, promoted cell proliferation and protected cells from apoptosis. Further experiments using in silico prediction, luciferase reporter assay and western blot assay demonstrated that miR-185 directly targeted SOCS3 by binding to its 3'-UTR. On the contrary to miR-185's protective effects, SOCS3 significantly suppressed functions of ß-cell and inactivated Stat3 pathway. When treating cells with miR-185 mimics in combination with SOCS3 overexpression plasmid, the inhibitory effects of SOCS3 were reversed. While combined treatment of miR-185 mimics and SOCS3 siRNA induced synergistically promotive effects compared to either miR-185 mimics or SOCS3 siRNA treatment alone. Moreover, we observed that miR-185 level was inversely correlated with SOCS3 expression in diabetes patients. In conclusion, this study revealed a functional and mechanistic link between miR-185 and SOCS3 in the pathogenesis of diabetes. MiR-185 plays an important role in the regulation of insulin secretion and ß-cell growth in diabetes. Restoration of miR-185 expression may serve a potentially promising and efficient therapeutic approach for diabetes.

Detection of human papillomavirus and expression of osteopontin in cervical cancer specimens.

To understand human papillomavirus (HPV) and expression of osteopontin (OPN) in cervical diseased tissues, HPV infection was detected in paraffin-embedded specimens of cervical lesions from 90 patients with cervical cancer. Three polymerase chain reaction (PCR) techniques were used to determine the detectable rate of HPV infection. Expression of HPV OPN protein was detected using immunohistochemical methods. When a pairwise comparison was made among the three PCR methods, χ2 analysis indicated P>0.05 for detection through the methods of MY09/11 and GP5+/6+, and P>0.05 through the methods of MY09/11 and Nested-PCR. This indicated that there was no statistically significant difference in the HPV infection detection sensitivity of these methods. However, χ2 comparison of the methods of GP5+/6+ and Nested-PCR indicated P<0.05, which demonstrated that there was a statistically significant difference. The rate of positive HPV DNA measured with Nested-PCR was significantly higher than that measured using the GP5+/6+ PCR method. The HPV OPN protein is expressed in cervical cancer, and the HPV OPN polypeptide antibody has broad spectrum reaction capacity and significant multivalence for HPV infection. Immunohistochemical detection was performed on tissue specimens using the purified rabbit HPV OPN polypeptide antibody. Sixty-one cases exhibited a positive result and 29 a negative result. The total rate of positive detection was 67.78%. HPV OPN may therefore serve as a candidate target for tumor treatment, including targeted therapies and vaccine development.

The anti-atherosclerotic effects of puerarin on induced-atherosclerosis in rabbits.

BACKGROUND: Cardiovascular disease is a major health issue worldwide, which has been well treated by the extracts of traditional herbs. Radix Puerariae, the dried root of the leguminous plant Pueraria lobata (Willd.) Ohwi, is a delicious vegetable in some southern provinces of China. Puerarin has also been widely used to treat human diseases, but few controlled studies are available. AIM: To determine the anti-atherosclerotic effects of puerarin on fat diet-induced atherosclerosis (AS) in rabbits. METHODS: An AS model was established by feeding 60 rabbits a high-fat diet and randomly dividing them into 6 groups: (1) normal control, (2) a model group (3) the statin, simvastatin and groups (4), (5) and (6) received 3 different amounts of puerarin. The fasting sera of all animals were collected before and after 90 days treatment to determine the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C). The aortas were pathomorphologically examined. PCNA and PDGF-A protein levels were assessed by Western blot. RESULTS: On the 90th day, the levels of TC, TG and LDL-C were significantly lower in high- and middle-dose puerarin groups and simvastatin group than in the model group (P<0.05), and the HDL-C level was higher. The percentages of plaque area to the total aortic area differed significantly for high- and middle-dose puerarin groups, simvastatin group and model group (P<0.05). Whole blood viscosity increased in the high-fat diet groups, while those in the treatment groups (except for the low-dose puerarin group) were significantly lower than those in the model group (P<0.05). PCNA and PDGF-A protein expression levels of rabbit aorta were low in the normal group. Protein expression levels in the groups fed the high-fat diet were significantly increased (P<0.05), but those in the high-dose puerarin group and simvastatin group were significantly decreased compared with the model group (P<0.05). CONCLUSIONS: Puerarin inhibits the formation and development of AS plaque and suppresses the migration and reproduction of vascular smooth muscle cells by decreasing PCNA and PDGF-A expressions in the rabbit. This is encouraging in terms of cardiovascular disease prevention/treatment.

Pentraxin 3, long expression in mononuclear cells of patients with acute coronary syndrome: Correlation with C-reactive protein and matrix metalloproteinase-9 levels.

OBJECTIVES: To investigate expression of pentraxin 3, long (PTX3) in patients with acute coronary syndrome (ACS) and its correlation with matrix metalloproteinase-9 (MMP-9) and C-reactive protein (CRP) levels. METHODS: Patients with ACS were randomly assigned to the ACS group (subdivided into unstable angina pectoris [UAP] and acute myocardial infarction [AMI]). Healthy participants and patients with stable angina pectoris (SAP) were enrolled as controls. Mononuclear cell PTX3 expression, and serum MMP-9 and CRP levels, were measured by enzyme-linked immunosorbent assay. RESULTS: The ACS group comprised 200 patients (80 in the UAP subgroup; 120 in the AMI subgroup). The control group comprised 130 participants (80 healthy volunteers and 50 patients with SAP). PTX3 expression was significantly higher in the ACS group compared with controls (3.64 ± 0.49 versus 1.85 ± 0.65 ng/ml), and significantly higher in the AMI compared with the UAP subgroup (5.44 ± 0.47 versus 3.39 ± 0.59 ng/ml). Serum MMP-9 and CRP levels were significantly higher in the ACS group compared with controls (48.55 ± 14.22 versus 23.14 ± 0.62 ng/ml; 4.88 ± 1.76 versus 1.26 ± 0.19 ng/ml, respectively), and significantly higher in the AMI compared with the UAP subgroup (58.13 ± 7.24 versus 31.77 ± 3.61 ng/ml; 5.80 ± 1.46 versus 3.27 ± 0.83 ng/ml, respectively). PTX3 expression, and MMP-9 and CRP levels in the SAP subgroup, were not significantly different from the healthy participants. PTX3 expression positively correlated with MMP-9 and CRP levels. CONCLUSIONS: In patients with ACS, peripheral blood mononuclear cell PTX3 expression, and serum MMP-9 and CRP levels, were significantly enhanced compared with controls; in addition, PTX3 expression positively correlated with MMP-9 and CRP levels. PTX3 may be involved in ACS pathogenesis.

Correlation between miR-23a and onset of hepatocellular carcinoma.

BACKGROUND AND AIMS: To clarify the role of miR-23a in the onset and development of hepatocarcinoma on the cellular, genetic and molecular levels. PATIENTS AND METHODS: Seventy-eight patients were included after hepatectomy. Relationships between the clinical pathological factors of tumor and paracancerous tissues were analyzed. Risk factors of overall and recurrence-free survival rates were subject to multi-variable analysis. Tissues were sequenced by digital miRNA expression profiling, and new miRNA was subject to target gene prediction. RESULTS: miR-23a expression was correlated with the stage of the TNM Classification of Malignant Tumours most significantly, followed by tumor size (P=0.041 and 0.047). High miR-23a, vascular invasion, tumor size≥7cm, tumor capsule and late pathological stage were the risk factors of overall survival rate, and those of recurrence-free survival rate also included alpha-fetoprotein level≥200µg/L and multiple tumors. Compared with normal hepatic cell line L-02, the miR-23a expression levels in tumor cell lines SMMC-7721 and HepG2 were up-regulated and down-regulated respectively. Transfecting miR-23a inhibitor suppressed cell growth. Apoptotic rates of the control and those transfected with inhibitor-NC and miR-23a inhibitor for 48h were similar. CONCLUSION: High miR-23a expression is the independent prognostic factor of overall and recurrence-free survival rates, and miR-23a may be involved in the onset of hepatocarcinoma as an oncogene.

Correlation between the Xba I polymorphism of apoB gene and serum lipid profiles in Li ethnic group.

OBJECTIVE: To study correlation between the Xba I polymorphism of apoB gene and plasma lipid profiles in Li ethnic group. METHODS: Total 151 cases of healthy Li people were recruited randomly by cluster sampling and 200 Han people were recruited as control; blood was drawn to analyze Xba I polymorphism distribution of apoB gene and serum lipid levels. RESULTS: There were lower serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in serum of Li people; while, high density lipoprotein cholesterol (HDL-C), X-/X+ genotype and X+ allele frequencies exhibited higher levels than Han people. Interestingly, HDL-C level was reduced, while LDL-C level was enhanced in subjects carrying heterozygous (X-/X+) genotype compared to homozygous (X-/X-) genotype. Additionally, there were no difference in serum level of triglyceride, TC, apoprotein A (apo A) and apoprotein B (apo B) between Li and Han people, the same results were showed between X-/X+ and X-/X- genotype carriers. CONCLUSIONS: Xba I polymorphism of apoB gene is correlated to the profiles of serum lipid level, X-/X+ genotype carriers are phenotyped with higher LDL-C level and lower level of HDL-C in Li ethnic group.

EPC-derived microvesicles protect cardiomyocytes from Ang II-induced hypertrophy and apoptosis.

Cell-released microvesicles (MVs) represent a novel way of cell-to-cell communication. Previous evidence indicates that endothelial progenitor cells (EPCs)-derived MVs can modulate endothelial cell survival and proliferation. In this study, we evaluated whether EPC-MVs protect cardiomyocytes (CMs) against angiotensin II (Ang II)-induced hypertrophy and apoptosis. The H9c2 CMs were exposed to Ang II in the presence or absence of EPC-MVs. Cell viability, apoptosis, surface area and ß-myosin heavy chain (ß-MHC) expression were analyzed. Meanwhile, reactive oxygen species (ROS), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS), and their phosphorylated proteins (p-Akt, p-eNOS) were measured. Phosphatidylinositol-3-kinase (PI3K) and NOS inhibitors were used for pathway verification. The role of MV-carried RNAs in mediating these effects was also explored. Results showed 1) EPC-MVs were able to protect CMs against Ang II-induced changes in cell viability, apoptosis, surface area, ß-MHC expression and ROS over-production; 2) The effects were accompanied with the up-regulation of Akt/p-Akt and its downstream eNOS/p-eNOS, and were abolished by PI3K inhibition or partially blocked by NOS inhibition; 3) Depletion of RNAs from EPC-MVs partially or totally eliminated the effects of EPC-MVs. Our data indicate that EPC-MVs protect CMs from hypertrophy and apoptosis through activating the PI3K/Akt/eNOS pathway via the RNAs carried by EPC-MVs.

Analysis of some common pathogens and their drug resistance to antibiotics.

OBJECTIVE: To investigate the common bacterial resistance of clinical isolates in our hospital in the second half of 2011. METHODOLOGY: Pathogens isolated from clinical samples in the second half of 2011 were analyzed and categorized to perform susceptibility tests. RESULTS: In the gram-negative bacteria, Enterobacteriaceae and non-fermenting gram-negative bacilli accounted for 55.89% and 34.51%. In the gram-positive bacteria, Staphylococcus aureus, Coagulase-negative staphylococci, Enterococcus, Strptococcus pneumonia accounted for 32.85%, 40.39%, 12.41% and 10.22%, respectively. Other species accounted for 4.14%. Klebsiella pneumonia and Pseudomonas aeruginosa were sensitive to cepoperazon, cefepime and imipenem. However,Acinetobacter baumannii was more sensitive to carbapenems antibiotics, which was followed by fourth generation cephalosporins. Klebsiella pneumoniae was extremely sensitive to amikacin, cefepime and imipenem, but was resistant to ampicillin. The detection rates of the broad-spectrum Escherichia coli, Pseudomonasaeruginosa and Klebsiella pneumoniae were 54.51%, 52.08% and 38.65%. The gram negative bacilli were the prevalent clinical pathogens in our hospital in the second half of 2011. CONCLUSION: The drug resistance of pathogenic bacteria has increased significantly recently, thus the surveillance of antibacterial agents is necessary, and rational use of antibiotic will be urgently needed to reduce the production and dissemination of drug resistant strains.