ABSTRACT
Related studies have shown that ITGB2 mediates mitochondrial glycolytic transformation in cancer-associated fibroblasts and participates in tumor occurrence, metastasis and invasion of cancer cells. Based on these studies, we tried to construct a mitochondrial glycolysis regulatory network and explored its effect on mitochondrial homeostasis and ovarian cancer cells' cancerous characteristics. Our research revealed a distinct increase in the expression of ITGB2 and associated signaling pathway elements (PI3K-AKT-mTOR) in cases of ovarian cancer. ITGB2 might control mTOR expression via the PI3K-AKT pathway, thus promote mitochondrial glycolysis transformation and cell energy supply in ovarian cancer. This pathway could also inhibit mitophagy, maintain mitochondrial stability, and enhance the cancerous characteristics in case of ovarian cancer cells by mediating mitochondrial glycolytic transformation. Thus, we concluded that ITGB2-associated signaling route (PI3K-AKT-mTOR) may contribute to the progression of cancerous traits in ovarian cancer via mediating mitochondrial glycolytic transformation.
Subject(s)
Ovarian Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Female , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Ovarian Neoplasms/pathology , TOR Serine-Threonine Kinases/metabolism , Glycolysis , Cell ProliferationABSTRACT
Multidrug resistance severely limits the efficacy of ovarian cancer (OC) treatment. Recent studies have revealed the carcinogenic role of LINC00707 RNA. However, the role of LINC00707 in the development of multidrug resistance in OC has not been clarified. Therefore, the aim of this study was to investigate the relationship between LINC00707 and multidrug resistance in OC, which can facilitate the development of new therapeutic agents for effectively addressing this issue. The RNA expression of LINC00707, miR-382-5p and leucine-rich repeat kinase 2 (LRRK2) in SKOV3 (a human OC cell line) cells was detected by qRT-PCR. The effects of LINC00707 on the proliferation and viability of SKOV3 cells were determined by MTT assay and colony formation assay. The interaction of LINC00707, miR-382-5p, and LRRK2 was bioinformatically predicted and verified with dual-luciferase reporter assay. In addition, the effect of LINC00707 on drug resistance in SKOV3 cells through targeting the miR-382-5p/LRRK2 axis was explored. The expression of LINC00707 and LRRK2 was significantly increased in SKOV3 cells, while miR-382-5p expression was significantly decreased. The results of bioinformatic prediction and colony formation assay demonstrated that LINC00707 could regulate LRRK2 expression in SKOV3 cells by targeting miR-382-5p. Additionally, knockdown of LINC00707 markedly increased expression of miR-382-5p and decreased that of LRRK2, increased cell proliferation and viability, as well as sensitivity to chemotherapeutic agents in SKOV3 cells. Notably, these manifestations were more obvious with simultaneous knockdown of LINC00707 and miR-382-5p compared with knockdown of LINC00707 alone. LINC00707 is overexpressed in SKOV3 cells and promotes SKOV3 cell proliferation and resistance to chemotherapeutic drugs via targeting the miR-382-5p/LRRK2 axis.
Subject(s)
MicroRNAs , Ovarian Neoplasms , RNA, Long Noncoding , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Line, Tumor , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Cell Proliferation/genetics , Drug Resistance, Multiple/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/geneticsABSTRACT
The removal of organic pollutants using green environmental photocatalytic degradation techniques urgently need high-performance catalysts. In this work, a facile one-step hydrothermal technique has been successfully applied to synthesize a Nb2O5 photocatalyst with uniform micro-flower structure for the degradation of methyl orange (MO) under UV irradiation. These nanocatalysts are characterized by transmission and scanning electron microscopies (TEM and SEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method, and UV-Vis diffuse reflectance spectroscopy (DRS). It is found that the prepared Nb2O5 micro-flowers presents a good crystal phases and consist of 3D hierarchical nanosheets with 400-500 nm in diameter. The surface area is as large as 48.6 m2 g-1. Importantly, the Nb2O5 micro-flowers exhibit superior catalytic activity up to 99.9% for the photodegradation of MO within 20 mins, which is about 60-fold and 4-fold larger than that of without catalysts (W/O) and commercial TiO2 (P25) sample, respectively. This excellent performance may be attributed to 3D porous structure with abundant catalytic active sites.
ABSTRACT
Efferocytosis, which is known as the phagocytic clearance of dying cells by professional as well as non-professional phagocytes, including a great number of intracellular/extracellular factors and signals, is interrelated with the immune system, contributing to local and systemic homeostasis, especially in tissues with high constitutive rates of apoptosis. Accumulating studies have indicated that immune dysregulation is associated with the pathogenesis of the female reproductive system, which causes preeclampsia (PE), recurrent spontaneous abortion (RSA), ruptured ectopic pregnancy, and so on. And some studies have revealed the pleiotropic and essential role of efferocytosis in these obstetrical disorders. More specifically, the occurrence and development of these diseases were in connection with some efferocytosis-related factors and signals, such as C1q, MBL, and IL-33/ST2. In this review, we systematically review the diverse impacts of efferocytosis in immune system and discuss its relevance to normal and pathological pregnancy. These findings may instruct future basic researches as well as clinical applications of efferocytosis-related factors and signals as latent predictors or therapeutic targets on the obstetrical disorders.
Subject(s)
Apoptosis/immunology , Phagocytes/immunology , Phagocytosis/immunology , Pregnancy Complications/immunology , Pregnancy/immunology , Abortion, Habitual/immunology , Animals , Female , Humans , Interleukin-33/immunology , Interleukin-33/metabolism , Macrophages/immunology , Mannose-Binding Protein-Associated Serine Proteases/immunology , Membrane Glycoproteins/immunology , Phagocytes/cytology , Phagocytosis/physiology , Pre-Eclampsia/immunology , Pregnancy Complications/pathology , Pregnancy, Ectopic/immunology , Receptors, Complement/immunologyABSTRACT
BACKGROUND: Accumulating documents have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis. As an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1) has been identified to be involved in the progression of many types of cancers. However, the biological function of NEAT1 in cervical cancer is not fully investigated. The aim of this study was to disclose the specific biological function of lncRNA NEAT1 in cervical cancer progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to identify the expression of lncRNA NEAT1 in the cervical cancer tissues and cell lines. All cervical cancer samples used in this study were collected from the Affiliated Suzhou Hospital of Nanjing Medical University between September 2012 and September 2017. The correlation between NEAT1 expression and the overall survival rate of cervical cancer patients was analyzed by Kaplan-Meier analysis. The effects of NEAT1 knockdown or overexpression on cell proliferation were tested by performing MTT assays and colony formation assays. Transwell assays were conducted to detect the migratory ability of cervical cancer cells, in which NEAT1 was silenced or overexpressed. Western blotting was utilized to validate whether NEAT1 promotes cervical cancer progression through activating PI3K-Akt signaling pathway. RESULTS: High expression of NEAT1 predicted poor prognosis of cervical cancer patients (χ2 = 0.735, P = 0.005). Knockdown of NEAT1 decreased the number of colonies in CaSki cell from 136.667 ± 13.503 to 71.667 ± 7.506 (t = -18.76, P = 0.003) and decreased the number of colonies in HeLa cell from 128.667 ± 13.317 to 65.667 ± 7.024 (t = -5.54, P = 0.031). However, overexpression of NEAT1 increased the number of colonies in SiHa cell from 84.667 ± 12.014 to 150.667 ± 18.037 (t = 7.27, P = 0.018). Knockdown of NEAT1 decreased the migratory number of CaSki cell from 100.333 ± 9.866 to 58.333 ± 5.859 (t = -8.08, P = 0.015) and reduced the migratory number in HeLa cell from 123.667 ± 12.097 to 67.667 ± 7.095 (t = -6.03, P = 0.026). Overexpression of NEAT1 increased the migratory number of SiHa cell from 127.333 ± 16.042 to 231.333 ± 31.786 (t = 4.92, P = 0.039). CONCLUSION: NEAT1 may exert oncogenic function in cervical cancer and serve as a novel therapeutic target for cervical cancer.
Subject(s)
Phosphatidylinositol 3-Kinases/physiology , RNA, Long Noncoding/physiology , Uterine Cervical Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Female , HeLa Cells , Humans , Middle AgedABSTRACT
PROBLEM: To explore whether IL-33/ST2 axis modulates the polarization and efferocytosis of decidual macrophages (dMφs). METHOD OF STUDY: The phenotype characteristics of dMφs from both normal pregnant women and recurrent spontaneous abortion (RSA) patients were determined by real-time polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Then, the efferocytosis and expression of IL-33 and its receptor (ST2) in dMφs were analyzed by FCM. Finally, the effects of sST2, a decoy receptor for IL-33 that inhibits the IL-33/ST2 signaling pathway, on the polarization and efferocytosis of dMφs and human macrophage cell line U937 were investigated. RESULTS: Compared with normal pregnancy, dMφs from RSA patients presented a M1 phenotype with high secretion of IL-33, whereas the expression of ST2 decreased. However, dMφs from RSA patients possessed a more powerful efferocytosis ability to clear the apoptotic decidual stromal cells (DSCs) compared with dMφs from normal pregnancy patients. Treatment with recombinant human sST2 led to the up-regulation of M1 bias and efferocytosis ability of both normal dMφs and U937. CONCLUSION: This study indicates that IL-33 secreted by dMφs promotes M2 bias at the feto-maternal interface, and as a result, RSA might attribute to the disturbance of IL-33/ST2 axis and the enhancement of efferocytosis of dMφs subsequently.
Subject(s)
Abortion, Habitual/metabolism , Abortion, Spontaneous/metabolism , Interleukin-1 Receptor-Like 1 Protein/metabolism , Interleukin-33/metabolism , Macrophages/metabolism , Macrophages/pathology , Phagocytosis/physiology , Abortion, Habitual/pathology , Abortion, Spontaneous/pathology , Adult , Apoptosis/physiology , Cell Line, Tumor , Female , Humans , Pregnancy , Signal Transduction/physiology , Stromal Cells/metabolism , Stromal Cells/pathology , U937 Cells , Up-Regulation/physiologyABSTRACT
BACKGROUND: Sirolimus-eluting stents (SES) with a biodegradable polymer coating have demonstrated promising results but have not been compared to SES with a durable polymer in high-risk patients. We compared the efficacy of these 2 stent types in patients with acute myocardial infarction (STEMI). METHODS: One thousand one hundred ninety-two STEMI patients were randomized to receive SES coated with biodegradable (n = 596) or durable polymer (n = 596). The study end-point was the composite of major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction (MI), or target lesion revascularization (TLR) at 1-year follow-up. Secondary end-points included individual components of primary end-point and stent thrombosis. RESULTS: Compared with durable polymer SES, the noninferiority of SES with biodegradable polymer coating was established by an absolute risk difference of 0.9% in the primary end-point (12.4% vs. 13.3%, P = 0.67) and an upper limit of one-sided 95% confidence interval (CI) of 2.96% (P for noninferiority = 0.001). Rate of death, recurrent MI, and TLR were 7.9% and 8.6% (HR: 0.92; 95% CI: 0.61-1.38, P = 0.67), 2.9% and 3.5% (HR: 0.80; 95% CI: 0.42-1.54, P = 0.51), and 2.0% and 3.2% (HR: 0.62; 95% CI: 0.30-1.30, P = 0.20) in the biodegradable polymer SES and durable polymer SES group at 1-year clinical follow-up, respectively. Despite similar rates of 30-day ARC definite/probable stent thrombosis, late stent thrombosis (stent thrombosis occurring beyond 30 days) was lower with biodegradable polymer SES (0.7% vs. 2.2%, P = 0.028). CONCLUSIONS: In patients undergoing primary PCI for STEMI, the use of biodegradable polymer SES was associated with noninferior 1-year rates of MACE compared with durable polymer SES.
Subject(s)
Absorbable Implants , Drug-Eluting Stents , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/methods , Sirolimus/administration & dosage , Electrocardiography , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate the application value of magnetic resonance diffusion-weighted imaging (DWI) combined with routine T2WI sequence in the determination of pathological complete response (pCR) after neoadjuvant therapy for rectal cancer. METHODS: Clinical data of 51 cases with locally advanced mid-low rectal cancer undergoing neoadjuvant therapy plus radical resection in the Rectal Cancer Center at The Sixth Affiliated Hospital of Sun Yat-sen University from June 2012 to April 2013 were analyzed retrospectively. Magnetic resonance DWI and T2WI sequences scanning were performed within 1 week before neoadjuvant therapy and within 1 week before operation. Routine single T2WI sequence and DWI combined with T2WI sequence were used separately to predict the residual tumor and to compare with postoperative pathological examination. The prediction values of two methods were compared. RESULTS: Of 51 patients, 12 cases had pathological complete response (pCR). Prediction of DWI combined T2WI sequence was correct in 8 cases of pCR, whose sensitivity and specificity were higher than those of routine single T2WI sequence (66.7%, 94.9% vs. 33.3%, 84.6%). Prediction value of DWI combined T2WI sequence for pCR was significantly higher as compared to routine single T2WI sequence (AUC, 0.808 vs. 0.590, P=0.001). CONCLUSION: Compared with the routine single T2WI sequence, DWI combined with T2WI sequence can improve the prediction accuracy of pathological complete response.
Subject(s)
Diffusion Magnetic Resonance Imaging , Rectal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Predictive Value of Tests , Rectal Neoplasms/therapy , Retrospective Studies , Sensitivity and SpecificityABSTRACT
AIM: To characterize the prevalence of hepatitis C virus (HCV) infection among Chinese intravenous drug users (IDUs). METHODS: A total of 432 adult IDUs (95 women and 337 men) in Shanghai were included in the study. The third-generation Elecsys Anti-HCV assay (Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305, Mannheim, Germany) was used to screen for antibodies against HCV. The RIBA strip, a supplemental anti-HCV test with high specificity, was performed on all of the samples that tested positive during the initial screening. All of the anti-HCV positive samples were analyzed with a Cobas TaqMan 48 Analyzer (Roche Diagnostics) for direct detection of HCV RNA. All of the HCV RNA-positive samples were sequenced for genotype determination. RESULTS: The preliminary screening identified 262 (60.6%) subjects who were seropositive for HCV. Of the 62 females and 200 males seropositive subjects, 16 (16.7%) and 65 (19.3%), respectively, were confirmed by RIBA, yielding an overall HCV seropositive rate of 18.8%. Four female (6.5%) and 14 male (7.0%) subjects tested positive for HCV RNA, indicating an active infection rate of 4.2% for the entire study population. The 18 HCV RNA-positive serum samples were genotyped. Seven individuals were genotype 1b, and four were genotype 1a. One individual each was infected with genotypes 2a, 2b and 3a. Four subjects were co-infected with multiple strains: two with genotypes 1a and 2a, and two with genotypes 1b and 2a. The active infection rate among HCV-seropositive individuals was 22.2%, which was significantly lower than most estimates. CONCLUSION: The prevalence of HCV is relatively low among IDUs in Shanghai, with a spontaneous recovery rate much higher than previous estimates.
Subject(s)
Drug Users/statistics & numerical data , Hepatitis C/epidemiology , Heroin Dependence/epidemiology , Urban Health/statistics & numerical data , Adult , Biomarkers/blood , China/epidemiology , Female , Genotype , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis C/blood , Hepatitis C/diagnosis , Hepatitis C Antibodies/blood , Humans , Male , Middle Aged , Prevalence , RNA, Viral/blood , Seroepidemiologic StudiesABSTRACT
BACKGROUND: No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI. METHODS: A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%. RESULTS: In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P < 0.05). CONCLUSIONS: An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.
Subject(s)
Electrocardiography , Fibrinolytic Agents/therapeutic use , Myocardial Infarction/drug therapy , Percutaneous Coronary Intervention , Tyrosine/analogs & derivatives , Urokinase-Type Plasminogen Activator/therapeutic use , Adult , Aged , Female , Humans , Logistic Models , Male , Middle Aged , Myocardial Infarction/physiopathology , Tirofiban , Tyrosine/therapeutic use , Ventricular Function, LeftABSTRACT
BACKGROUND: Transradial access has been increasingly used during primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI) in last decade. Clinical benefits of upstream use of tirfiban therapy in STEMI patients treated by primary PCI have been reported. We investigated the merits of transradial vs. transfemoral access in primary PCI for STEMI patients with upstream use of tirofiban. METHODS: Patients with STEMI treated with tirofiban between December 2006 and October 2012 then by primary PCI were compared between transradial (n = 298) and transfemoral (n = 314) access. Baseline demographics, angiographic and PCI features and primary endpoint of major adverse cardiac events (MACE) at 30-day clinical follow-up were recorded. RESULTS: Baseline and procedural characteristics were comparable between the two groups, apart from more patients in transradial group had hypertension and were treated by thrombus aspiration during primary PCI. Significantly fewer MACE occurred in the transradial group (5.4%) compared with the transfemoral group (9.9%) at 30-day clinical follow-up. Major bleeding events at 30-day clinical follow-up were 0 in transradial group and in 2.9% of transfemoral group. Multivariate analysis confirmed transradial approach as an independent negative predictor of 30-day MACE (HR 0.68; 95%CI 0.35 - 0.91; P = 0.03). CONCLUSIONS: Using transradial approach in primary PCI for acute STEMI infarction patients treated with tirofiban was clearly beneficial in reducing bleeding complications and improving 30-day clinical outcomes.
Subject(s)
Myocardial Infarction/drug therapy , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/methods , Tyrosine/analogs & derivatives , Aged , Angioplasty, Balloon, Coronary , Female , Humans , Male , Middle Aged , Tirofiban , Tyrosine/therapeutic useABSTRACT
The effect of bisoprolol on dendritic cell (DC) migration was investigated, including the analysis of protein expression, cytokine secretion and activation of the PI3K-pathway. The chemotactic cell numbers in cholesterol-loaded DCs treated with epinephrine were significantly decreased by 26.66±6.29% (6h), 35.67±2.91% (12h) and 29.33±1.09% (24h). This effect was significantly reversed by 46.00±10.65% (6h), 64.25±6.77% (12h) and 55.74±5.51% (24h) when bisoprolol and epinephrine were both present. In cholesterol-loaded DCs, treatment with epinephrine significantly increased AR-ß1 protein expression by 56.99±4.87%, but inhibited ß-arrestin 2 and CCR7 protein expression by 30.51±4.22% and 25.31±0.04%, respectively. These effects were reversed by bisoprolol by 36.87±4.40%, 41.47±3.95% and 30.14±0.54%, respectively. TNF-α and MMP9 levels were decreased by 68.33±4.00% and 39.57±9.21% in cholesterol-loaded DCs treated with epinephrine. In contrast, when bisoprolol and epinephrine were administered together, the secretion of these proteins was significantly increased by 233.81±37.06 % and 76.66±14.21%, respectively. Treatment with epinephrine decreased PI3K-phosphorylation by 31.88±2.79%, 40.24±5.69% and 30.93±4.66% at 15, 30 and 60min, respectively, whereas the effect of epinephrine on the expression of phosphorylated PI3K was reversed by 49.49±12.12%, 70.93±16.14% and 47.62±6.00%, respectively, when cells were treated with both bisoprolol and epinephrine. Wortmannin inhibited the effects of bisoprolol on PI3K-phosphorylation (38.63±6.12%), the expression of CCR7 (23.4±2.72%), the secretion of TNF-α (69.46±4.48%) and MMP9 (43.15±4.63%), and the number of chemotactic cells (36.84±5.22%). This is the first study to establish a signaling pathway, epinephrine-AR-ß1-ß-arrestin2-PI3K-MMP9/CCR7, which plays a critical role in the migration of DCs.
Subject(s)
Arrestins/metabolism , Bisoprolol/pharmacology , Chemotaxis/drug effects , Dendritic Cells/drug effects , Epinephrine/pharmacology , Receptors, CCR7/metabolism , Adrenergic beta-1 Receptor Antagonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Androstadienes/pharmacology , Atherosclerosis/metabolism , Cell Movement/drug effects , Cholesterol/metabolism , Dendritic Cells/cytology , Flow Cytometry , Humans , Matrix Metalloproteinase 9/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Time Factors , Tumor Necrosis Factor-alpha/metabolism , Wortmannin , beta-Arrestin 2 , beta-ArrestinsABSTRACT
BACKGROUND: We investigated whether an additional intracoronary tirofiban bolus administration following upstream intravenous treatment could further improve myocardial reperfusion and clinical outcome in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 453 eligible STEMI patients were randomly allocated to intracoronary bolus administration of tirofiban (10 µg/kg; n=229) or saline (10 mL; n=224) during primary PCI, followed by intravenous tirofiban infusion (0.15 µg/kg/min) for 24-36 h. Serum levels of P-selectin, vWF, CD40L and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary bolus administration. The primary endpoint was ST-segment resolution (STR) at 90 min after the procedure. Second endpoints included corrected TIMI frame count (cTFC), left ventricular volumes and ejection fraction (EF), and major adverse cardiac events (MACE) at 30-day and 6-month follow-up. RESULTS: Intracoronary tirofiban administration resulted in a higher rate of completed STR (59.0% vs. 44.6%, P=0.002), lower cTFC (21.6±5.4 vs. 23.7±7.8, P=0.048), and significantly reduced coronary sinus levels of P-selectin, vWF, CD40L and SAA. Patients treated with intracoronary tirofiban had a trend toward less MACE at 30 days (3.1% vs. 6.7%, P=0.072). At 6 months, left ventricular end-systolic volume was smaller, EF was higher and MACE-free survival was improved (96.1% vs. 90.6%, P=0.020) in the intracoronary tirofiban group. CONCLUSIONS: An additional intracoronary tirofiban bolus administration following upstream intravenous treatment reduces coronary circulatory platelet activation and inflammatory process, and significantly improves myocardial reperfusion and left ventricular function as well as 6-month MACE-free survival for STEMI patients undergoing primary PCI.
Subject(s)
Myocardial Infarction/drug therapy , Myocardial Infarction/surgery , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/administration & dosage , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Tyrosine/analogs & derivatives , Aged , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Injections, Intra-Arterial , Male , Middle Aged , Myocardial Infarction/metabolism , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Tirofiban , Treatment Outcome , Tyrosine/administration & dosageABSTRACT
Current strategies to help tobacco smokers quit have limited success as a result of the addictive properties of the nicotine in cigarette smoke. We hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector expressing high levels of an anti-nicotine antibody would persistently prevent nicotine from reaching its receptors in the brain. To test this hypothesis, we constructed an AAVrh.10 vector that expressed a full-length, high-affinity, anti-nicotine antibody derived from the Fab fragment of the anti-nicotine monoclonal antibody NIC9D9 (AAVantiNic). In mice treated with this vector, blood concentrations of the anti-nicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine. The antibody shielded the brain from systemically administered nicotine, reducing brain nicotine concentrations to 15% of those in naïve mice. The amount of nicotine sequestered in the serum of vector-treated mice was more than seven times greater than that in untreated mice, with 83% of serum nicotine bound to immunoglobulin G. Treatment with the AAVantiNic vector blocked nicotine-mediated alterations in arterial blood pressure, heart rate, and locomotor activity. In summary, a single administration of a gene transfer vector expressing a high-affinity anti-nicotine monoclonal antibody elicited persistent (18 weeks), high titers of an anti-nicotine antibody that obviated the physiologic effects of nicotine. If this degree of efficacy translates to humans, AAVantiNic could be an effective preventative therapy for nicotine addiction.
Subject(s)
Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/therapeutic use , Dependovirus/genetics , Nicotine/immunology , Smoking Cessation/methods , Animals , Antibodies, Monoclonal/genetics , Male , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: Primary percutaneous coronary intervention (PCI) has been clearly identified as the first therapeutic option for patients with acute ST-segment elevation myocardial infarction (STEMI). The importance of reducing door-to-balloon (D2B) time has gained increased recognition. This study aimed to assess the feasibility, safety and efficacy of the strategy of direct ambulance transportation of patients with acute STEMI to catheterization lab to receive primary PCI. METHODS: The study population included 141 consecutive patients with chest pain and ST-segment elevation who were admitted to the catheterization laboratory directly by the ambulance and underwent primary PCI (DIRECT group). Another 145 patients with STEMI randomly selected from the PCI database, were served as control group (conventional group); they were transported to catheterization laboratory from emergency room (ER). The primary endpoint of D2B time, and secondary endpoint of in-hospital and 30-day major adverse cardiac events (MACE, including death, non-fatal reinfarction, and target vessel revascularization) were compared. RESULTS: Baseline and procedural characteristics between the two groups were comparable, except more patients in the DIRECT group presented TIMI 0-1 flow in culprit vessel at initial angiogram (80.1% and 73.8%, P = 0.04). Comparing to conventional group, the primary endpoint of D2B time was reduced ((54 ± 18) minutes and (112 ± 55) minutes, P < 0.0001) and the percentage of patients with D2B < 90 minutes was increased in the DIRECT group (96.9% and 27.0%, P < 0.0001). The success rate of primary PCI with stent implantation with final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was significantly higher in the DIRECT group (93.8% and 85.2%, P = 0.03). Although no significant difference was found at 30-day MACE free survival rate between the two groups (95.0% and 89.0%, P = 0.06), a trend in improving survival status in the DIRECT group was demonstrated by Kaplan-Meier analysis. CONCLUSION: Direct ambulance transport of STEMI patients to the catheterization laboratory could significantly reduce D2B time and improve success rate of primary PCI and 30-day clinical outcomes.
Subject(s)
Ambulances/statistics & numerical data , Angioplasty, Balloon, Coronary , Emergency Service, Hospital/statistics & numerical data , Myocardial Infarction/therapy , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Traditional reperfusion options for patients with acute ST-segment elevation myocardial infarction (STEMI) presenting to non-primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCI. A third option, involving interventionalist transfer, was examined in the REVERSE-STEMI study. METHODS AND RESULTS: A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were randomized to receive PPCI with either an interventionalist- (n=165) or a patient-transfer (n=169) strategy. The primary end point of door-to-balloon (D2B) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events (MACE) at 1-year clinical follow-up were compared between the 2 groups. Compared with the patient-transfer strategy, the interventionalist-transfer strategy resulted in a significantly shortened D2B time (median, 92 minutes versus 141 minutes; P<0.0001), with more patients having first balloon angioplasty within 90 minutes (21.2% versus 7.7%, P<0.001). This treatment strategy also was associated with higher left ventricular ejection fraction (0.60±0.07 versus 0.57±0.09, P<0.001) and improved 1-year MACE-free survival (84.8% versus 74.6%, P=0.019). Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE (hazard ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.003). CONCLUSIONS: The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital, particularly in a congested cosmopolitan region where patient transfers could be prolonged.
Subject(s)
Angioplasty, Balloon, Coronary , Electrocardiography , Hospital-Physician Relations , Myocardial Infarction/therapy , Patient Transfer , Technology Transfer , Aged , China , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Outcome Assessment, Health Care , Professional Practice , Proportional Hazards Models , Prospective Studies , Retrospective Studies , Stroke Volume/physiology , Survival Rate , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Randomized, controlled trials have demonstrated the superiority of sirolimus-eluting stent (SES) implantation during primary percutaneous coronary intervention (PCI), as opposed to bare-metal stents, in patients with ST-elevation myocardial infarction (STEMI). This study aimed to test the hypothesis that clinical benefits of SES treatment were independent of gender in this setting. METHODS: A total of 2042 patients with STEMI undergoing SES-based primary PCI were prospectively enrolled into Shanghai Acute Coronary Event (SACE) registry (1574 men and 468 women). Baseline demographics, angiographic and PCI features, and in-hospital and 30-day major adverse cardiac events (MACE) were analyzed as a function of gender. RESULTS: Compared with men, women were older and more frequently had hypertension, diabetes, and hypercholesterolemia. Use of platelet glycoprotein IIb/IIIa receptor inhibitor (GPI, 65.5% vs. 62.2%, P = 0.10) and procedural success rate (95.0% vs. 94.2%, P = 0.52) were similar in both genders. In-hospital death and MACE occurred in 3.8% and 7.6%, and 4.5% and 8.1% in the male and female patients, respectively (all P > 0.05). At 30-day follow-up, survival (94.3% vs. 93.8%, P = 0.66) and MACE-free survival (90.2% vs. 89.3%, P = 0.52) did not significantly differ between men and women. After adjustment for differences in patient demographics, angiographic and procedural features, there were no significant difference in either in-hospital (OR = 0.77, 95%CI of 0.48 to 1.22, P = 0.30) or 30-day mortality (OR = 1.28, 95%CI of 0.73 to 2.23, P = 0.38) between women and men. CONCLUSION: Despite more advanced age and clustering of risk factors in women, female patients with STEMI treated by SES-based primary PCI had similar in-hospital and short-term clinical outcomes as their male counterparts.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug-Eluting Stents , Myocardial Infarction/therapy , Sirolimus/therapeutic use , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary , China , Female , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Prospective Studies , Registries , Sex FactorsABSTRACT
The title compound, [Mg(C(10)H(8)N(2))(H(2)O)(4)](C(7)H(4)FO(2))(2), consists of a bivalent [Mg(C(10)H(8)N(2))(H(2)O)(4)](2+) cation and two 4-fluorbenzoate anions. In the complex cation, the Mg(II) atom is coordinated by two N atoms from a 2,2'-bipyridine ligand and four water O atoms in a distorted MgN(2)O(4) octa-hedral geometry. The Mg(II) atom is located on a twofold rotation axis and thus a cation exhibits C(2) mol-ecular symmetry. The 2,2'-bipyridine ligands exhibit nearly perfect planarity (r.m.s. deviations = 0.0061â Å). In the crystal, O-Hâ¯O and C-Hâ¯O hydrogen bonds link the cations and anions into a three-dimensional supra-molecular network.
ABSTRACT
BACKGROUND: Current guidelines support primary percutaneous coronary intervention (primary PCI) as the first treatment of choice (as opposed to thrombolytic therapy) for patients with acute ST-segment elevation myocardial infarction (STEMI) especially when delivered within 12 hours of symptom onset. We aimed to evaluate the impact of different clinical pathways on reduction of reperfusion delay and subsequent improvement in outcomes in patients with STEMI. METHODS: From November 2005 to November 2007, 546 consecutive patients with definite STEMI, who upon arrival at the emergency room were triaged to undergo primary PCI, were included. Of them, 271 patients were brought directly to catheterization laboratory (rapid group), and 275 patients were admitted to the coronary care unit (CCU) or cardiac ward first, and then transferred to the catheterization laboratory (non-rapid group). Primary endpoint was door-to-balloon (D2B) time, and secondary endpoints included infarct size assessed by peak CK-MB level and rates of major cardiac adverse events (MACE) including death, reinfarction, or target-vessel revascularization during hospitalization and at 30-day clinical follow-up. RESULTS: Baseline clinical characteristics, angiographic features and procedural success rates were comparable between the two groups, except that more patients received glycoprotein IIb/IIIa receptor inhibitors before angiography (84.0% and 77.1, P = 0.042) and had TIMI 3 flow in the culprit vessel at initial angiogram (17.1% and 9.2%, P = 0.007) in the non-rapid group. The D2B time was shortened ((108 +/- 44) minutes and (138 +/- 31) minutes, P < 0.0001), and number of patients with D2B time < 90 minutes was greater (22.6% and 10.9%, P < 0.0001) in the rapid group. The advantages associated with rapid intra-hospital transfer were enhanced if the patients presented to the hospital at regular hours. Peak CK-MB level was significantly reduced in the rapid group. In-hospital mortality (4.1% and 5.8%) and cumulative MACE rate (7.0% and 9.8%) did not significantly differ between rapid and non-rapid groups. At 30 days, cumulative death- and MACE-free survival rates were improved in the rapid group (94.5% and 89.5%, P = 0.035; 90.1% and 84.0%, P = 0.034, respectively). CONCLUSIONS: Clinical pathway with bypass of CCU/cardiac ward admission was associated with rapid reperfusion, smaller infarct size, and improved short-term survival for patients with STEMI undergoing primary PCI. In the future, it is essential to reduce the time delay for patients presenting at off-hours.