RESUMO
Photocatalysis with potentially low cost and sustainable utilization is a typically environmentally benign method for the degradation of organic pollutants, but the rational design and fabrication of photocatalysts with high catalytic performance is still an enormous challenge. The efficient segregation of photogenerated electron-hole pairs in photocatalysts is a key and essential factor to decide photocatalytic activity. Herein, a novel Step-scheme (S-scheme) heterojunction photocatalyst, a g-C3N4/Bi2MoO6 (g-CN/BMO) composite, was successfully fabricated using g-C3N4 nanosheet-wrapped Bi2MoO6 microspheres. By adjusting the amount of g-C3N4 in BMO, a series of g-CN/BMO composites was prepared while optimizing posttreatment temperature. The resulting g-CN/BMO indicated well the photocatalytic performance for the degradation of phenol and hydrogen evolution reactions, especially, 100 g of g-CN was integrated into 100 g of the pre-calcined BMO at 200 °C to produce 100% g-CN/BMO-200, showing the highest photocatalytic performance compared to single composite BMO, BMO-200, g-CN, and g-CN/BMO-200 with other mass ratios. Combining the results from the density functional theory calculations and the results of X-ray photoelectron spectroscopy, for S-scheme heterojunction-structured g-CN/BMO-200, the internal electric field-, band edge bending- and coulomb interaction-driven efficient segregation of photogenerated electrons and holes at the interface is elucidated to explain the photocatalytic mechanism, and the resulting holes on the VB of BMO and electrons on the CB of g-CN are responsible for the improvement of the photocatalytic performance. This study revealed that for the S-scheme g-CN/BMO composite the internal electric field, band edge bending and coulomb interaction at the interface between g-CN and BMO can not only promote the effective segregation of electrons and holes, but also retain stronger redox ability. Such an investigation provides a facile and simple strategy to fabricate novel S-scheme heterojunction-structured photocatalysts for solar energy conversion.
RESUMO
BACKGROUND: Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV) possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. METHODS: The ApoE-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67), senescence (p16INK4a), oxidant (NADPH oxidase 4, NOX4) and antioxidant (superoxide dismutase, SOD) were observed by immunofluorescence staining. RESULTS: Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE-/- mice. However, the decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS) in ApoE-/- mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53-apoptosis pathway and oxidant-antioxidants in the hearts of ApoE-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16INK4a in the hearts of ApoE-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. CONCLUSION: AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress.
Assuntos
Apolipoproteínas E/genética , Cardiomegalia/tratamento farmacológico , Cardiotônicos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Cardiomegalia/sangue , Cardiomegalia/genética , Cardiomegalia/patologia , Cardiotônicos/farmacologia , Feminino , Fibrose , Deleção de Genes , Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Saponinas/farmacologia , Transcriptoma/efeitos dos fármacos , Triterpenos/farmacologia , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/patologiaRESUMO
OBJECTIVES: This study aims to predict the risk of noise-induced hearing loss (NIHL) through a back-propagation neural network (BPNN) model. It provides an early, simple and accurate prediction method for NIHL. DESIGN: Population based, a cross sectional study. SETTING: Han, China. PARTICIPANTS: This study selected 3266 Han male workers from three automobile manufacturing industries. PRIMARY OUTCOME MEASURES: Information including personal life habits, occupational health test information and occupational exposure history were collected and predictive factors of NIHL were screened from these workers. BPNN and logistic regression models were constructed using these predictors. RESULTS: The input variables of BPNN model were 20, 16 and 21 important factors screened by univariate, stepwise and lasso-logistic regression. When the BPNN model was applied to the test set, it was found to have a sensitivity (TPR) of 83.33%, a specificity (TNR) of 85.92%, an accuracy (ACC) of 85.51%, a positive predictive value (PPV) of 52.85%, a negative predictive value of 96.46% and area under the receiver operating curve (AUC) is: 0.926 (95% CI: 0.891 to 0.961), which demonstrated the better overall properties than univariate-logistic regression modelling (AUC: 0.715) (95% CI: 0.652 to 0.777). The BPNN model has better predictive performance against NIHL than the stepwise-logistic and lasso-logistic regression model in terms of TPR, TNR, ACC, PPV and NPV (p<0.05); the area under the receiver operating characteristics curve of NIHL is also higher than that of the stepwise and lasso-logistic regression model (p<0.05). It was a relatively important factor in NIHL to find cumulative noise exposure, auditory system symptoms, age, listening to music or watching video with headphones, exposure to high temperature and noise exposure time in the trained BPNN model. CONCLUSIONS: The BPNN model was a valuable tool in dealing with the occupational risk prediction problem of NIHL. It can be used to predict the risk of an individual NIHL.
Assuntos
Automóveis , Perda Auditiva Provocada por Ruído , Indústria Manufatureira , Redes Neurais de Computação , Doenças Profissionais , Exposição Ocupacional , Humanos , Perda Auditiva Provocada por Ruído/diagnóstico , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Estudos Transversais , Masculino , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Medição de Risco/métodos , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Ruído Ocupacional/efeitos adversos , Modelos Logísticos , Fatores de Risco , Curva ROC , População do Leste AsiáticoRESUMO
Aim: The present study aimed at investigating associations of the platelet-to-monocyte ratio (PMR), a novel hematological indicator of inflammatory responses with 30-day outcomes in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). Methods: We recruited 329 patients with HBV-DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30-day mortality. Receiver operating characteristic curve analysis was performed to compare the predictive values of prognostic markers. Results: During the 30-day follow-up period, 21 (6.4%) patients died. The PMR was significantly different between nonsurvivors and survivors. Lower PMR was found to be associated with an increased risk of 30-day mortality, and PMR (odds ratio: 1.011; 95% CI: 1.003-1.019; P=0.005) was found to be an independent predictor of 30-day mortality in patients with HBV-DeCi with a significant predictive value (AUC = 0.826, 95% CI: 0.781-0.865). The combination of PMR and MELD score could improve prognostic accuracy in these patients (AUC = 0.911, 95% CI: 0.876-0.940). Conclusions: Our results demonstrate that low PMR may be an independent predictor of 30-day mortality in patients with HBV-DeCi, and combined with the MELD score, it may be useful to complement other conventional measures to enable effective management of these patients.
Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Estudos Retrospectivos , Monócitos , Cirrose Hepática/complicações , Prognóstico , Curva ROC , Hepatite B/complicaçõesRESUMO
Background: Tumor-specific protein 70 (SP70) was identified as a new biomarker associated with the proliferation and invasion of cancer cells. This study aimed to investigate the expression of SP70 in hepatocellular carcinoma (HCC) and assess its clinical value in the diagnosis and prediction of early HCC recurrence. Methods: A total of 1049 subjects from the First Affiliated Hospital of Nanjing Medical University were recruited in this study. Serum SP70, alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence II (PIVKA-II) were measured. The diagnostic performance for HCC was obtained using the receiver operating characteristic (ROC) curve, and recurrence-free survival (RFS) was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictive factors of RFS. Results: SP70 was highly expressed in HCC cells and HCC tissue. Serum SP70 levels in the HCC group were significantly higher than in the benign liver diseases group and healthy control group (P<0.001). SP70 combined with AFP showed the best diagnostic performance (AUC=0.909, 95%CI [confidence interval]=0.890-0.929). Kaplan-Meier analysis revealed that patients with high SP70 levels had shorter median RFS than those with low SP70 levels (P=0.003). In addition, high SP70 levels were significantly associated with shorter RFS (P=0.037) in the AFP-negative subgroup. Univariate and multivariate analyses confirmed that preoperative serum SP70 level, serum AFP, tumor diameter and microvascular invasion were independent prognostic factors of RFS. Conclusion: SP70 is a promising biomarker in diagnosing HCC. High preoperative serum SP70 level is associated with an increased risk of early relapse and could be used as a valuable marker to predict early recurrence of HCC after resection.
RESUMO
BACKGROUND: Astragaloside IV (As-IV) exerts beneficial effects on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury, possibly through normalization of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) function. The exact mechanisms remain unknown. This study was designed to investigate the role of protein kinase A (PKA) in the protective effect of As-IV on SERCA2a function. METHODS: Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation (H/R) with or without As-IV treatment. Myocyte injury was determined by the creatine kinase (CK)-MB fraction in supernatant. Myocardial SERCA2a activity and PKA kinase activity were assessed. PKA subunit mRNA expression and Ser(16) phosphorylated phospholamban (Ser(16)-PLN) protein expression were detected by real-time PCR and Western blot, respectively. RESULTS: The administration of As-IV significantly decreased CK-MB release and restored SERCA2a activity in H/R cardiomyocytes. The mRNAs of PKA subunits, PKA-RIα, PKA-RIIα, PKA-RIIß, PKA-Cα and PKA-Cß, were downregulated in H/R cardiomyocytes. However, PKA-Cα mRNA expression was significantly increased after As-IV treatment. Meanwhile, there was a tendency to recovery of the H/R-induced PKA kinase activity decrease after As-IV treatment. The expression of Ser(16)-PLN protein, which is specifically phosphorylated by PKA, was upregulated in As-IV-treated H/R cardiomyocytes. CONCLUSIONS: These results suggest that the cardioprotection of As-IV may be through the upregulation of PKA and Ser(16)-PLN, thereby restoring SERCA2a function in H/R injury.
Assuntos
Cardiotônicos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Creatina Quinase Forma MB/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Expressão Gênica/efeitos dos fármacos , Miócitos Cardíacos/patologia , Subunidades Proteicas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Traumatismo por Reperfusão/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
Genetic factors and gene-environment interaction may play an important role in the development of noise induced hearing loss (NIHL). 191 cases and 191 controls were selected by case-control study. Among them, case groups were screened from workers exposed to noise in binaural high-frequency hearing thresholds greater than 25 dB (A). Workers with hearing thresholds ≤ 25 dB (A) in any binaural frequency band were selected to the control group, based on matching factors such as age, exposure time to noise, and operating position. The blood samples from two groups of workers were subjected to DNA extraction and SNP sequencing of CASP3 and CASP7 genes using the polymerase chain reaction ligase detection reaction method. Conditional logistic regression correction was used to analyze the genetic variation associated with susceptibility to NIHL. There was an association between rs2227310 and rs4353229 of the CASP7 gene and the risk of NIHL. Compared with the GG genotype, the CC genotype of rs2227310 reduced the risk of NIHL. Compared with CC genotype, the TT genotype of rs4353229 reduced the risk of NIHL. Workers carrying the rs2227310GG and rs4353229CC genotype had an increased risk of NIHL compared to workers without any high-risk genotype. There were additive interaction and multiplication interaction between CASP7rs2227310 and CNE, and the same interaction between CASP7rs4353229 and CNE. The interaction between the CASP7 gene and CNE significantly increased the risk of NIHL. The genetic polymorphisms of CASP7rs2227310GG and CASP7rs4353229CC were associated with an increased risk of NIHL in Han Chinese population and have the potential to act as biomarkers for noise-exposed workers.
Assuntos
Etnicidade/genética , Perda Auditiva/genética , Ruído , Polimorfismo Genético , Adulto , Biomarcadores/metabolismo , Caspase 7/genética , China , Feminino , Humanos , Masculino , Exposição OcupacionalRESUMO
NJ001 is a monoclonal antibody that can specifically recognize the SP70 antigen on lung adenocarcinoma cells. The goal of this study was to explore its utility in targeted imaging. Subcutaneous xenograft and orthotopic lung tumor implantation BALB/c mouse models were established. Near-infrared fluorescent CF750-labeled NJ001 was injected into two tumor mouse models. Mice that received orthotopic lung tumor implantation were also injected with NJ001-conjugated nanomagnetic beads intravenously, and then underwent micro-CT scanning. Meanwhile, mice with lung tumor were intravenously injected with normal saline and bare nanomagnetic beads as a control. Fluorescence could be monitored in the mice detected by anti-SP70 fluorescence imaging, which was consistent with tumor burden. Signal intensities detected with SP70-targeted micro-CT scans were greater than those in control mice. More importantly, orthotopic tumor lesions could be found on the fourth week with SP70-targeted imaging, which was 2 weeks earlier than detection in the control. Our results suggest that SP70 is a promising target for molecular imaging, and molecularly targeted imaging with an NJ001-labeled probe could be applied for the early detection of lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico por imagem , Anticorpos Monoclonais/análise , Neoplasias Pulmonares/diagnóstico por imagem , Animais , Biomarcadores Tumorais/análise , Linhagem Celular Tumoral , Detecção Precoce de Câncer , Corantes Fluorescentes/análise , Humanos , Imunoconjugados/análise , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Molecular , Imagem ÓpticaRESUMO
BACKGROUND: Previously, we developed a monoclonal antibody (mAb) NJ001 that binds to the antigen SP70 in human non-small cell lung cancer (NSCLC) cells and showed it could inhibit lung adenocarcinoma (AD) growth. Here, we investigated the effect and mechanisms of NJ001 in lung AD metastasis. METHODS: Human lung AD cells (SPC-A1 and A549) were treated with different concentrations of mAb NJ001, and the effects of NJ001 on cell migration and invasive activity were investigated using wound-healing and Matrigel assays, respectively. The molecular mechanism of this inhibition was explored by microarrays, qRT-PCR, western blot, luciferase assays and electrophoretic mobility shift assays (EMSA). RESULTS: MAb NJ001 markedly suppressed lung AD cell migration; and the invasiveness of SPC-A1 and A549 cells treated with mAb NJ001 was diminished by 65%. Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) was highly expressed in SPC-A1 cells treated with mAb NJ001, whereas knockdown of TIMP-3 by shRNA significantly increased SPC-A1 and A549 invasiveness. MAb NJ001 affects lung AD by inhibiting TIMP-3 through direct transcriptional regulation of FOXP1 binding sites in the TIMP-3 promoter region, as shown in luciferase assays and EMSA. CONCLUSIONS: MAb NJ001 inhibits invasiveness and metastasis in lung AD through the FOXP1 binding sites in the TIMP-3 promoter region. It may have clinical applications in preventing and treating metastatic lung AD.
Assuntos
Adenocarcinoma de Pulmão/genética , Anticorpos Monoclonais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Pulmonares/genética , Proteínas Repressoras/metabolismo , Adenocarcinoma de Pulmão/patologia , Sítios de Ligação , Proliferação de Células , Humanos , Neoplasias Pulmonares/patologia , Inibidor Tecidual de Metaloproteinase-3 , TransfecçãoRESUMO
SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuron-specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression-free survival (PFS) were analyzed. Serum SP70 levels were significantly decreased after chemotherapy in the partial remission (PR) group (P < .001) and increased in the progressive disease (PD) group (P < .001), but not significantly changed in the stable disease (SD) group (P = .114). Although similar changes were observed on CEA and CYFRA21-1 levels but not NSE, ROC analysis demonstrated that SP70 is superior to the others. Additionally, patients with EGFR mutation had higher serum SP70 levels and tissue SP70 expression than patients without EGFR mutation (P = .014 and P = .002, respectively). The median PFS of patients with decreased SP70 levels after chemotherapy was longer than that of patients with stable or increased serum SP70 level (24 months vs 12 months vs 2 months, P < .001), and the differences of all other 3 tumor markers were not obvious. Serum SP70 is a sensitive and real-time indicator of chemotherapeutic efficacy in patients with advanced NSCLC and related to PFS.
RESUMO
Maghemite nanoparticles (MNPs) were synthesized by chemical coprecipitation and coated with meso-2,3-dimercaptosuccinic acid (HOOC-CH(SH)-CH(SH)-COOH or DMSA). The morphology and properties of the nanoparticles were characterized by TEM, XRD, Zeta Potential Analyzer and VSM. Subsequentially, the anti-human cardiac troponin I (cTnI) immunomagnetic nanoparticles (IMNPs) were prepared by grafting anti-human cTnI antibodies on the surface of DMSA-coated MNPs using the linker of EDC (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride). The conjugation amount of the antibodies and the activity of IMNPs was evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting. The results show that the physical and chemical adsorption occurred at the same time, but the former was unstable and apt to desorb, and the maximum conjugation amount of antibody was about 96 microg on the 0.1 mg MNPs by covalent bond. The stability was also investigated, and after 300 days the antibodies on the IMNPs remained the biological activity.
Assuntos
Anticorpos/química , Nanopartículas/química , Troponina I/imunologia , Anticorpos/imunologia , Western Blotting , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Nanotecnologia/métodos , Succímero/químicaRESUMO
In clinical practice, Astragali Radix (Astragalus), the root of Astragalus membranaceus Bunge, has been widely applied to treat patients with viral diseases, including viral myocarditis in China. The present study was designed to evaluate the protective effects of Astragalus on the function of sarcoplasmic reticulum calcium ATPase (SERCA2) activity and endothelin system at acute and chronic periods of myocarditis mice induced by CVB(3) infection. Astragalus feeding (2.2 mg/kg/day) could significantly increase the survival rate, alleviate pathological alterations and serum cardiac troponin I (cTnI), as well as restore impaired SERCA activity at the acute stage. Low affinity and capacity of ETR were reversed with Astragalus after the first CVB(3) inoculation up to 7 days and after the second virus inoculation up to 150 days. In the meantime, the contents of cardiac ET-1 and ANP were reduced. Comparison the myocarditis mice treated with Perindopril (0.44 mg/kg/day), an ACE inhibitor, shows that Astragalus achieved a similar effect on survival rate, SERCA2 and ET system. These results indicated that the beneficial effects of Astragalus and Perindopril for treating viral myocarditis might be partly mediated by preserving the functions of SERCA 2 activity and ET system.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Astrágalo/química , Cardiotônicos/farmacologia , Miocardite/fisiopatologia , Perindopril/farmacologia , Viroses/fisiopatologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Myeloperoxidase (MPO), a leukocyte hemoprotein released from neutrophils, is thought to be a potential participant in plaque formation and plaque rupture. Therefore, MPO is regarded as an early marker predicting the risk for atherosclerosis, especially for coronary artery disease and acute coronary syndrome. We generated hybridoma clones 1E3 and 3E8 secreting monoclonal antibodies (mAbs) specific to human MPO. BALB/c mice were immunized with MPO protein purified from human neutrophils. Splenocytes from these mice were fused with the mouse myeloma cell line SP2/0. Based on isotyping of the mAbs, both clones 1E3 and 3E8 were referred to the IgG1 subclass. The specificities of 1E3 and 3E8 were assessed by enzyme-linked immunosorbent assay (ELISA), and only 3E8 was confirmed by western blot. We developed a simple MPO-immunosorbent assay (MPO-ISA) on microplate based on both the immune activity and peroxidase activity of MPO. The mAb secreted by clone 3E8 was chosen as coating antibody to capture the plasma MPO without interfering with the peroxidase activity of MPO. Then, tetramethylbenzidine substrate was added to the microwell directly, catalyzed by captured MPO, and a colored product was formed. The simple MPO-ISA test has a sensitivity of 3.68 ng/mL. The linear concentration of MPO-ISA for commercial MPO standard ranged to 250 ng/mL. The average recovery rate is 101.02%. The imprecision within-day was <10% at three different MPO levels. The imprecision between-day was <10% at low and middle MPO levels and varied to 14.61% at the high MPO level. We found that the established MPO-ISA can detect the plasma MPO from human and cavy, but not from mouse and rat. Compared with the commercial human MPO ELISA assay, the MPO-ISA can be used to detect the natural human MPO protein, but not recombinant MPO polypeptides. The generated mAbs and MPO-ISA test may be useful tools to assess risk for inflammation and cardiac events.
Assuntos
Anticorpos Monoclonais/imunologia , Ensaio de Imunoadsorção Enzimática , Imunoadsorventes/imunologia , Peroxidase/imunologia , Animais , Especificidade de Anticorpos , Regulação Enzimológica da Expressão Gênica/imunologia , Humanos , Camundongos , RatosRESUMO
PURPOSE: The purpose of this study was to determine whether different initiation of exercise training (ET) produces different effect sizes for left ventricular (LV) remodeling and cardiopulmonary rehabilitation in patients with LV dysfunction after myocardial infarction (MI). METHOD: Trials evaluating ET outcomes identified by searches in OVID MEDLINE, EMBASE, PubMed and WEB OF SCIENCE were used. Meta-analysis was conducted with the use of the software STATA 11.0. The results were expressed as the standardized mean difference (SMD), with corresponding 95% CI and p value. RESULTS: The largest changes in LV remodeling and cardiopulmonary capacity rehabilitation were obtained when programs began the acute phase after MI. With the healing of MI, the beneficial effects of ET on LV ejection fraction (LVEF), LV end-systolic diameter (LVDs) and peak VO2 were gradually weakened even worse. The incidence of major adverse cardiac events was not significantly increased in acute phase post-MI. Sensitivity analyses show that ET still had significant effect in reducing LVDs and increasing peak VO2, while ET no longer had statistical effect in increasing LVEF but showed favorable trends when the same research institution's works were excluded. CONCLUSIONS: ET has favorable effects on LV remodeling and cardiopulmonary rehabilitation in LV dysfunction post-MI patients. The greatest benefits are obtained when ET starts at the acute phase following MI. IMPLICATIONS FOR REHABILITATION: Early exercise training is safe and feasible in acute and healing phase after myocardial infarction. Early exercise training could attenuate LV remodeling and improve cardiopulmonary capacity in patients with myocardial infarction after hospital discharge (around one week post-MI). Exercise training has favorable effects on LV remodeling and cardiopulmonary capacity rehabilitation. Exercise training should be treated to have the same roles with drugs in secondary prevention of myocardial infarction.
Assuntos
Terapia por Exercício/métodos , Infarto do Miocárdio/complicações , Disfunção Ventricular Esquerda/reabilitação , Remodelação Ventricular , Exercício Físico , Humanos , Viés de Publicação , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Gold nanoparticles are emerging as promising biomedical tools due to their unique nanoscale characteristics. Our purpose was to synthesize a hollow-shaped gold nanoparticle and to investigate its effect on human aortic endothelial cells (HAECs) in vitro. Hollow gold nanoshells with average 35-nm diameters and 10-nm shell thickness were obtained by galvanic replacement using quasi-spherical nanosilver as sacrifice-template. Our results showed that hollow gold nanoshells in the culture medium could be internalized into the cytoplasm of HAECs. No cytotoxicity effect of hollow gold nanoshells on HAECs was observed within the test concentrations (0-0.8 µg/mL) and test exposure period (0-72 h) by tetrazolium dye assay. Meanwhile, the release of cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without hollow gold nanoshells). The concentrations of vasodilators, nitric oxide, and prostacyclin I-2 were not changed, but the vasoconstrictor endothelin-1 was decreased by hollow gold nanoshells treatment in HAECs. HAECs exposed to hollow gold nanoshells resulted in suppressing expressions of genes involved in apoptosis and activating expressions of genes of adhesion molecules. Moreover, we demonstrated by in vitro endothelial tube formation that hollow gold nanoshells (0.8 µg/mL) could not inhibit angiogenesis by the HAECs. Altogether, these results indicate that the structure and major function of HAECs would not be disrupted by hollow gold nanoshell treatment.
RESUMO
This work presented a rapid, inexpensive, reliable, and flexible quantitative immunoassay for cardiac troponin I (cTnI). The assay was based on the concepts of one-step dual monoclonal antibody "sandwich" principle, the low density protein array, the nanogold probe, and the silver enhancement on the gold particles. The capture antibody (IgG1) coated supporting nitrocellulose membrane and the colloidal gold-labeled detection antibody (cAu-IgG2) were prepared before the detection. The detection procedure involved two steps, i.e., immunoreaction and silver amplification. The assay needs only small amounts of serum samples of patients, The whole detection procedure of the assay could be fulfilled within 40 min (much faster than the routine enzyme-linked immunosorbent assay (ELISA) that takes usually at least 3 hours for a turnaround test). The detection results could be easily imaged with a simple flatbed scanner or even observed with the naked eye. The assay showed good specific response to cTnI with very little cross-reactivity to the skeletal isoforms of troponin I (sTnl), cardiac troponin T (cTnT), and myoglobin (Mb). A cut-off value of 0.3 ng/ml was obtained from a reference control group (200 normal serum samples). 588 patients' serum samples were assayed simultaneously by routine ELISA and this colloidal gold method to test the validity of the method. The data were analyzed using the statistical package SPSS version 11.0 (SPSS Inc.) There was no significant difference between these two assays (P = 0.66 > 0.05). The agreement between this method (> or < 0.3 ng/ml) and ELISA was 86%.
Assuntos
Colorimetria/métodos , Miocárdio/química , Troponina I/análise , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Espectrofotometria UltravioletaRESUMO
Angiotensin II (Ang II)-induced mitochondrial dysfunction is a prominent characteristic of the majority of cardiovascular diseases. Astragaloside IV (As-IV), the major active ingredient of Astragalus membranaceus (Fisch.) Bge. (a traditional Chinese herbal medicine), possesses antioxidant properties. The present study was carried out to examine whether As-IV can reverse Ang II-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs) and to elucidate the underlying molecular mechanisms. Cultured rat aortic VSMCs treated with Ang II (1 µM) for 24 h exhibited mitochondrial dysfunction, including a decrease in mitochondrial oxygen consumption rates (OCRs), adenosine triphosphate (ATP) production and mitochondrial DNA (mtDNA) levels, as well as the disruption of mitochondrial structural integrity. Following treatment with Ang II, As-IV (50 µg/ml) was added to the culture medium followed by incubation for a further 24 h. The administration of As-IV significantly increased the mitochondrial OCRs, ATP production and the mtDNA levels, and reversed the mitochondrial morphological changes which occurred in the VSMCs. Treatment with As-IV also reversed the Ang II-induced increase in the production of reactive oxygen species (ROS), the increase in NADPH oxidase and xanthine oxidase activity, as well as the decrease in mitochondrial membrane potential (ΔΨm) and manganese superoxide dismutase (Mn-SOD) activity. Furthermore, treatment with As-IV led to an increase in the mRNA expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and mitochondrial transcription factor A (Tfam), and in the protein expression of PGC-1α, parkin and dynamin 1-like protein 1 (Drp1) in the VSMCs. These results indicate that As-IV exerts beneficial effects on Ang II-induced mitochondrial dysfunction in rat VSMCs and that these effects are mediated through the inhibition of ROS overproduction, as well as the promotion of mitochondrial autophagy and mitochondrial biogenesis. These data demonstrate the antioxidant properties of As-IV.
Assuntos
Angiotensina II/efeitos adversos , Doenças Mitocondriais/induzido quimicamente , Doenças Mitocondriais/tratamento farmacológico , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/metabolismo , Células Cultivadas , DNA Mitocondrial/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , NADPH Oxidases/metabolismo , Oxirredução/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismoRESUMO
Cardiac troponin I (cTnI) is the only sarcomeric protein identified to date that is expressed exclusively in cardiac muscle. Its expression in cancer tissues has not been reported. Herein, we examined cTnI expression in non-small cell lung cancer (NSCLC) tissues, human adenocarcinoma cells SPCA-1 (lung) and BGC 823 (gastric) by immunohistochemistry, western blot analysis and real-time PCR. Immunopositivity for cTnI was demonstrated in 69.4% (34/49) NSCLC tissues evaluated, and was strong intensity in 35.3% (6/17) lung squamous cell carcinoma cases. The non-cancer-bearing lung tissues except tuberculosis (9/9, 100%) showed negative staining for cTnI. Seven monoclonal antibodies (mAbs) against human cTnI were applied in immunofluorescence. The result showed that the staining pattern within SPCA-1 and BGC 823 was dependent on the epitope of the cTnI mAbs. The membrane and nucleus of cancer cells were stained by mAbs against N-terminal peptides of cTnI, and cytoplasm was stained by mAbs against the middle and C-terminal peptides of cTnI. A ~25 kD band was identified by anti-cTnI mAb in SPCA-1 and BGC 823 extracts by western blot, as well as in cardiomyocyte extracts. The cTnI mRNA expressions in SPCA-1 and BGC 823 cells were about ten thousand times less than that in cardiomyocytes. Our study shows for the first time that cTnI protein and mRNA were abnormally expressed in NSCLC tissues, SPCA-1 and BGC 823 cells. These findings challenge the conventional view of cTnI as a cardiac-specific protein, enabling the potential use of cTnI as a diagnostic marker or targeted therapy for cancer.
Assuntos
Adenocarcinoma/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Neoplasias Gástricas/metabolismo , Troponina I/metabolismo , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Reação em Cadeia da Polimerase em Tempo Real , Estômago/patologia , Neoplasias Gástricas/patologia , Troponina I/genéticaRESUMO
Interleukin-26 (IL-26) is one of the cytokines secreted by Th17 cells whose role in human tumors remains unknown. Here, we investigated the expression and potential role of IL-26 in human gastric cancer (GC). The expression of IL-26 and related molecules such as IL-20R1, STAT1 and STAT3 was examined by real-time PCR and immunohistochemisty. The effects of IL-26 on cell proliferation and cisplatin-induced apoptosis were analyzed by BrdU cooperation assay and PI-Annexin V co-staining, respectively. Lentiviral mediated siRNA was used to explore its mechanism of action, and IL-26 related signaling was analyzed by western blotting. Human GC tissues showed increased levels of IL-26 and its related molecules and activation of STAT3 signaling, whereas STAT1 activation did not differ significantly between GC and normal gastric tissues. Moreover, IL-26 was primarily produced by Th17 and NK cells. IL-26 promoted the proliferation and survival of MKN45 and SGC-7901 gastric cancer cells in a dose-dependent manner. Furthermore, IL-20R2 and IL-10R1, which are two essential receptors for IL-26 signaling, were expressed in both cell lines. IL-26 activated STAT1 and STAT3 signaling; however, the upregulation of the expression of Bcl-2, Bcl-xl and c-myc indicated that the effect of IL-26 is mediated by STAT3 activation. Knockdown of STAT1 and STAT3 expression suggested that the proliferative and anti-apoptotic effects of IL-26 are mediated by the modulation of STAT1/STAT3 activation. In summary, elevated levels of IL-26 in human GC promote proliferation and survival by modulating STAT1/STAT3 signaling.
Assuntos
Interleucinas/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucinas/genética , Interleucinas/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Células Th17/efeitos dos fármacos , Células Th17/metabolismoRESUMO
One major obstacle for successful application of nanoparticles in medicine is its potential nanotoxicity on the environment and human health. In this study, we evaluated the cytotoxicity effect of dimercaptosuccinic acid-coated iron oxide (DMSA-Fe2O3) using cultured human aortic endothelial cells (HAECs). Our results showed that DMSA-Fe2O3 in the culture medium could be absorbed into HAECs, and dispersed in the cytoplasm. The cytotoxicity effect of DMSA-Fe2O3 on HAECs was dose-dependent, and the concentrations no more than 0.02 mg/ml had little toxic effect which were revealed by tetrazolium dye assay. Meanwhile, the cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without DMSA-Fe2O3). However, the endocrine function for endothelin-1 and prostacyclin I-2, as well as the urea transporter function, was altered even without obvious evidence of cell injury in this context. We also showed by real-time PCR analysis that DMSA-Fe2O3 exposure resulted in differential effects on the expressions of pro- and anti-apoptosis genes of HAECs. Meanwhile, it was noted that DMSA-Fe2O3 exposure could activate the expression of genes related to oxidative stress and adhesion molecules, which suggested that inflammatory response might be evoked. Moreover, we demonstrated by in vitro endothelial tube formation that even a small amount of DMSA-Fe2O3 (0.01 and 0.02 mg/ml) could inhibit angiogenesis by the HAECs. Altogether, these results indicate that DMSA-Fe2O3 have some cytotoxicity that may cause side effects on normal endothelial cells.