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1.
J Environ Public Health ; 2023: 9065729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396032

RESUMO

In recent years, with the development of 'China's new urbanization, the "characteristic town movement" with the development of industrial economy first has brought problems to a large number of rural settlements, such as no cultural planning, no consumption of industry, and no soul. Then, in reality, there are still a large number of rural settlements under the planning of the upper-level local government, with the goal of developing into a characteristic town in the future. Therefore, this study believes that there is an urgent need to build a framework for evaluating the construction potential of rural settlements with sustainable characteristic towns. Not only that but also a decision analysis model should be provided for real-world empirical cases. This model needs to cover the assessment of the sustainable development potential of characteristic towns as the goal and the formulation of improvement strategies. This study combines the data collection of current characteristic town development rating reports, applies data exploration technology to extract core impact elements and obtain hierarchical decision rules, integrates expert domain knowledge with DEMATEL technology, and establishes an impact network relationship diagram between core impact elements. At the same time, the representative characteristic town cases are assessed for their sustainable development potential, and the modified VIKOR technique is applied to clarify the actual problems of the empirical cases, in an attempt to determine whether the development potential and development plan of the characteristic town meet the sustainable development needs from the pre-evaluation mechanism.


Assuntos
Desenvolvimento Sustentável , Urbanização , Humanos , Cidades , População Rural , Planejamento Social
2.
ACS Appl Mater Interfaces ; 15(20): 24437-24447, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37150934

RESUMO

Various phosphonic acid based self-assembled monolayers (SAMs) have been commonly used for interface modifications in inverted perovskite solar cells. This typically results in significant enhancement of the hole extraction and consequent increase in the power conversion efficiency. However, the surface coverage and packing density of SAM molecules can vary, depending on the chosen SAM material and underlying oxide layer. In addition, different SAM molecules have diverse effects on the interfacial energy level alignment and perovskite film growth, resulting in complex relationships between surface modification, efficiency, and lifetime. Here we show that ethanolamine surface modification combined with [2-(9H-carbazol-9-yl)ethyl]phosphonic acid (2PACz) results in significant improvement in device stability compared to devices with 2PACz modification only. The significantly smaller size of ethanolamine enables it to fill any gaps in 2PACz coverage and provide improved interfacial defect passivation, while its different chemical structure enables it to provide complementary effects to 2PACz passivation. Consequently, the perovskite films are more stable under illumination (slower photoinduced segregation), and the devices exhibit significant stability enhancement. Despite similar power conversion efficiencies (PCE) between 2PACz only and combined ethanolamine-2PACz modification (PCE of champion devices ∼21.6-22.0% for rigid and ∼20.2-21.0% for flexible devices), the T80 lifetime under simulated solar illumination in ambient is improved more than 15 times for both rigid and flexible devices.

3.
ArXiv ; 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37033459

RESUMO

Diagnosis of adverse neonatal outcomes is crucial for preterm survival since it enables doctors to provide timely treatment. Machine learning (ML) algorithms have been demonstrated to be effective in predicting adverse neonatal outcomes. However, most previous ML-based methods have only focused on predicting a single outcome, ignoring the potential correlations between different outcomes, and potentially leading to suboptimal results and overfitting issues. In this work, we first analyze the correlations between three adverse neonatal outcomes and then formulate the diagnosis of multiple neonatal outcomes as a multi-task learning (MTL) problem. We then propose an MTL framework to jointly predict multiple adverse neonatal outcomes. In particular, the MTL framework contains shared hidden layers and multiple task-specific branches. Extensive experiments have been conducted using Electronic Health Records (EHRs) from 121 preterm neonates. Empirical results demonstrate the effectiveness of the MTL framework. Furthermore, the feature importance is analyzed for each neonatal outcome, providing insights into model interpretability.

4.
PLoS One ; 18(2): e0281402, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36749752

RESUMO

BACKGROUND: Sunitinib was approved several years ago as a first-line drug for treating metastatic renal cell carcinoma (mRCC); however, its high price and broad side effects when administered at the standard dose have limited its clinical use. A clinical trial (NCT02072031) confirmed that anlotinib could be used as the first-line treatment for mRCC. This study was conducted to evaluate the cost-effectiveness of anlotinib as a first-line treatment for mRCC compared to that of sunitinib in China. METHODS: A Markov model was established to compare the cost-effectiveness of anlotinib with that of sunitinib. Clinical data were obtained from a multi-center phase II trial (clinical trial information: NCT02072031). Utility values were obtained from the literature. Total costs were calculated from a Chinese societal perspective. A sensitivity analysis was conducted to assess the model uncertainty. The life-year (LY), quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio were calculated. RESULTS: The base-case analysis over a lifetime horizon of 10 years showed that the anlotinib group had 2.196 LYs and 1.487 QALYs at a total cost of $68,597.84. The sunitinib group had 2.194 LYs and 1.432 QALYs at a total cost of $88,060.02. This resulted in incremental cost-effectiveness ratios (ICER) of anlotinib versus sunitinib of $-9,210,858.93 per LYs and $-354,117.07 per QALYs, suggesting that anlotinib is a more effective and less costly strategy than sunitinib. CONCLUSION: Anlotinib may be a more cost-effective first-line treatment strategy for mRCC than sunitinib in China.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Sunitinibe/uso terapêutico , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Análise de Custo-Efetividade , Análise Custo-Benefício , China , Anos de Vida Ajustados por Qualidade de Vida
5.
IEEE Trans Pattern Anal Mach Intell ; 45(3): 2667-2681, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35679387

RESUMO

Unsupervised learning is just at a tipping point where it could really take off. Among these approaches, contrastive learning has led to state-of-the-art performance. In this paper, we construct a novel probabilistic graphical model that effectively incorporates the low rank promoting prior into the framework of contrastive learning, referred to as LORAC. In contrast to the existing conventional self-supervised approaches that only considers independent learning, our hypothesis explicitly requires that all the samples belonging to the same instance class lie on the same subspace with small dimension. This heuristic poses particular joint learning constraints to reduce the degree of freedom of the problem during the search of the optimal network parameterization. Most importantly, we argue that the low rank prior employed here is not unique, and many different priors can be invoked in a similar probabilistic way, corresponding to different hypotheses about underlying truth behind the contrastive features. Empirical evidences show that the proposed algorithm clearly surpasses the state-of-the-art approaches on multiple benchmarks, including image classification, object detection, instance segmentation and keypoint detection. Code is available: https://github.com/ssl-codelab/lorac.

6.
Cancer Biol Ther ; 23(1): 1-8, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36154909

RESUMO

Defects in tRNA expressions and modifications had been linked to various types of tumorigenesis and progression in recent studies, including colorectal cancer. In the present study, we evaluated transcript levels of mitochondrial tyrosyl-tRNA synthetase YARS2 in both colorectal cancer tissues and normal colorectal tissues using qRT-PCR. The results revealed that the mRNA expression level of YARS2 in colorectal cancer tissues was significantly higher than those in normal intestinal tissues. Knockdown of YARS2 in human colon cancer cell-line SW620 leads to significant inhibition of cell proliferation and migration. The steady-state level of tRNATyr, OCR, and ATP synthesis were decreased in the YARS2 knockdown cells. Moreover, our data indicated that inhibition of YARS2 is associated with increased reactive oxygen species levels which sensitize these cells to 5-FU treatment. In conclusion, our study revealed that targeting YARS2 could inhibit colorectal cancer progression. Thus, YARS2 might be a carcinogenesis candidate gene and can serve as a potential target for clinical therapy.


Assuntos
Neoplasias Colorretais , Tirosina-tRNA Ligase , Trifosfato de Adenosina , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila , Humanos , Mutação , RNA Mensageiro , RNA de Transferência de Tirosina , Espécies Reativas de Oxigênio , Tirosina-tRNA Ligase/genética , Tirosina-tRNA Ligase/metabolismo
7.
Org Lett ; 24(5): 1146-1151, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35112867

RESUMO

A novel photo-thermo-mechanochemical approach to assembling quinolines catalyzed by iron(II) phthalocyanine has been realized for the first time. This transformation features a cost-efficient catalytic system and operational simplicity, is free of solvent, and shows good substrate tolerance, providing a green alternative to existing thermal approaches. Mechanistic experiments demonstrate that the in-situ-formed secondary amine may be the key intermediate for the further cyclization/aromatization process.

8.
ACS Mater Au ; 2(3): 215-236, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-36855381

RESUMO

With the progress in the development of perovskite solar cells, increased efforts have been devoted to enhancing their stability. With more devices being able to survive harsher stability testing conditions, such as damp heat or outdoor testing, there is increased interest in encapsulation techniques suitable for this type of tests, since both device architecture compatible with increased stability and effective encapsulation are necessary for those testing conditions. A variety of encapsulation techniques and materials have been reported to date for devices with different architectures and tested under different conditions. In this Perspective, we will discuss important factors affecting the encapsulation effectiveness and focus on the devices, which have been subjected to outdoor testing or damp heat testing. In addition to encapsulation requirements for these testing conditions, we will also discuss device requirements. Finally, we discuss possible methods for accelerating the testing of encapsulation and device stability and discuss the future outlook and important issues, which need to be addressed for further advancement of the stability of perovskite solar cells.

9.
Front Public Health ; 9: 610280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046384

RESUMO

Background: The COVID-19 global pandemic has posed unprecedented challenges to health care systems all over the world. The speed of the viral spread results in a tsunami of patients, which begs for a reliable screening tool using readily available data to predict disease progression. Methods: Multicenter retrospective cohort study was performed to develop and validate a triage model. Patient demographic and non-laboratory clinical data were recorded. Using only the data from Zhongnan Hospital, step-wise multivariable logistic regression was performed, and a prognostic nomogram was constructed based on the independent variables identifies. The discrimination and calibration of the model were validated. External independent validation was performed to further address the utility of this model using data from Jinyintan Hospital. Results: A total of 716 confirmed COVID-19 cases from Zhongnan Hospital were included for model construction. Men, increased age, fever, hypertension, cardio-cerebrovascular disease, dyspnea, cough, and myalgia are independent risk factors for disease progression. External independent validation was carried out in a cohort with 201 cases from Jinyintan Hospital. The area under the curve (AUC) was 0.787 (95% confidence interval [CI]: 0.747-0.827) in the training group and 0.704 (95% CI: 0.632-0.777) in the validation group. Conclusions: We developed a novel triage model based on basic and clinical data. Our model could be used as a pragmatic screening aid to allow for cost efficient screening to be carried out such as over the phone, which may reduce disease propagation through limiting unnecessary contact. This may help allocation of limited medical resources.


Assuntos
COVID-19 , Humanos , Modelos Logísticos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Triagem
10.
Phytomedicine ; 85: 153547, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33812170

RESUMO

BACKGROUND: Colon cancer treatments include surgery, radiotherapy, and chemotherapy. Chemotherapy using 5-fluorouracil (5-FU) has been widely applied to treat colorectal cancer (CRC). However, it is important to explore the use of chemotherapy drugs in combination with other agents to decrease severe adverse effects. PURPOSE: This study aimed to investigate the effects of curcumin in combination with 5-FU on the proliferation, migration, and apoptosis of CRC SW620 cell line both in vitro and in vivo. METHODS: Flow cytometry was used to study the effect of curcumin on chemotherapy-induced apoptosis in CRC cells. The mechanism of curcumin's enhanced antitumor effect in vivo was investigated using gene knockdown, TUNEL, western blot, qRT-PCR and immunohistochemistry. RESULTS: The results showed a synergistic effect of the two compounds on CRC cells. Considerable reduction in the proliferation and migration of SW620 cells was observed in the combination treatment group. Significantly increased apoptosis rate extended the survival of immunodeficient mice in the combination group as compared to that of the 5-FU group (p < 0.05). The results showed that curcumin significantly inhibited pERK signaling and downregulated L1 expression in SW620 cells. CONCLUSIONS: We conclude that curcumin promotes chemosensitivity of CRC cells to 5-FU by downregulating L1 expression. Our findings provide experimental evidence for the synergism between curcumin and 5-FU, which can be utilized in clinical applications for reducing the toxicity and adverse effects of 5-FU.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Curcumina/farmacologia , Fluoruracila/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Sinergismo Farmacológico , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Camundongos , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Chem Commun (Camb) ; 55(21): 3121-3123, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30793154

RESUMO

Introduction of lattice strain into catalysts is a facile way to modify catalytic behaviour. Here, we report the synthesis of Pd nanoparticles with compressive strain by pulsed laser ablation of a Pd target immersed in an aqueous solution. The intensive quenching effect induces obvious compressive strain which improves the ORR performance of the Pd nanoparticles significantly.

12.
Curr Neurovasc Res ; 14(4): 323-329, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29076429

RESUMO

BACKGROUND: Recent studies have provided evidence that microRNAs (miRNAs), as a potential biomarker, were involved in the regulation of gene expression in Myocardial Infarction (MI). This study aimed to highlight the role of salvianolate on cardiomyocyte apoptosis in MI. METHODS: Anterior descending branch of left coronary artery was ligated to set up MI model. MiR- 122-5p mimic was transfected into cardiomyocytes and verified by quantitative real-time PCR (qRT-PCR). Cell viability and apoptotic rate were measured by MTT assay and flow cytometry together with TUNEL method, respectively. Changes in the expression of caspase-3, Bax and Bcl-2 were quantified by qRT-PCR and western blot. RESULTS: After treatment with salvianolate, miR-122-5p expression and caspases-3 activity significantly decreased in rat myocardial tissues. Furthermore, cardiomyocytes apoptosis rate was obviously suppressed while cell viability dramatically increased in H9C2 cardiomyocytes. However, overexpression of miR-122-5p reversed the aforementioned trends. Simultaneously, it could also mitigate the anti-apoptosis effect of salvianolate on the upregulation of caspases-3 viability and Bax expression and downregulation of Bcl-2 expression. CONCLUSION: Salvianolate induces the anti-apoptosis mechanism of cardiomyocytes via downregulation of miR-122-5p, Bax expression and caspases-3 as well as upregulation of Bcl-2 expression. In contrast, overexpression of miR-122-5p inhibits the effect of salvianolate.


Assuntos
Apoptose/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Extratos Vegetais/uso terapêutico , Animais , Apoptose/fisiologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Células Cultivadas , Regulação para Baixo/fisiologia , MicroRNAs/antagonistas & inibidores , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
13.
Oncotarget ; 8(35): 59915-59928, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28938693

RESUMO

Atherosclerosis is an inflammatory disease regulated by several immune cells including lymphocytes, macrophages and dendritic cells. Gut probiotic bacteria like Lactobacilli have been shown immunomodificatory effects in the progression of atherogenesis. Some Lactobacillus stains can upregulate the activity of regulatory T-lymphocytes, suppress T-lymphocyte helper (Th) cells Th1, Th17, alter the Th1/Th2 ratio, influence the subsets ratio of M1/M2 macrophages, inhibit foam cell formation by suppressing macrophage phagocytosis of oxidized low-density lipoprotein, block the activation of the immune system with dendritic cells, which are expected to suppress the atherosclerosis-related inflammation. However, various strains can have various effects on inflammation. Some other Lactobacillus strains were found have potential pro-atherogenic effect through promote Th1 cell activity, increase pro-inflammatory cytokines levels as well as decrease anti-inflammatory cytokines levels. Thus, identifying the appropriate strains is essential to the therapeutic potential of Lactobacilli as an anti-atherosclerotic therapy.

14.
J Electrocardiol ; 50(5): 686-689, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28623015

RESUMO

Myocardial perforation by pacemaker electrode is a very serious complication. Usually, the pacemaker electrode perforates the right ventricle, but rarely the left ventricular myocardium. We describe an 82-year-old female patient who presented with left ventricular pacing after temporary pacemaker implantation and was diagnosed with myocardial perforation. Emergency thoracotomy showed that the exact position of the cardiac perforation was close to the left ventricular apex. Perforation of the left ventricular free wall by an electrode sometimes progresses slowly. We should be alert to the possibility of left ventricular perforation, in which case, immediate surgery is the best option.


Assuntos
Ventrículos do Coração/lesões , Marca-Passo Artificial/efeitos adversos , Idoso de 80 Anos ou mais , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/terapia , Eletrocardiografia , Feminino , Ventrículos do Coração/cirurgia , Humanos , Doença Iatrogênica , Toracotomia
15.
Int J Cardiol ; 228: 666-671, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27883979

RESUMO

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is seen to be mostly elevated in patients with acute heart failure (AHF). However, cases of AHF presenting with low NT-proBNP levels have been reported. In this study designed to investigate the factors associated with low NT-proBNP levels in AHF patients, we discovered that etiology and related factors have an influence on NT-proBNP levels. METHODS: In this study, 154 AHF patients met the study criteria (117 men, median age 74years; left ventricular ejection fraction [LVEF] 46±13%; New York Heart Association [NYHA] classes II-IV). We analyzed the different clinical variables of patients based on plasma NT-proBNP levels. In addition, we identified the differences in NT-proBNP levels between ischemic and non-ischemic etiologies, as well as the relationships between time from symptom onset to ED visit and NT-proBNP levels. RESULTS: The group with low NT-proBNP levels showed an ischemic association, higher LVEF, lower NYHA class and shorter time from symptom onset to ED visit. Plasma NT-proBNP levels were lower in the ischemic group than in the non-ischemic group (P<0.01). Meanwhile, NT-proBNP levels were relatively low in patients during early phases of AHF hospitalization and increased with time from symptom onset to ED visit (P<0.01). CONCLUSION: We inferred that low NT-proBNP levels may infer the ischemic etiology especially in patients with normal LVEF in the early phases of AHF hospitalization.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Volume Sistólico
16.
Medicine (Baltimore) ; 95(41): e5113, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27741130

RESUMO

BACKGROUND: It is well known that cardiologists empirically judge the culprit lesion of acute ST-segment elevation myocardial infarction (STEMI) according to the corresponding electrocardiographic leads. However, In addition to the obstruction of left anterior descending (LAD) coronary artery, rare cases with the occlusion of proximal right coronary artery (RCA) and/or isolated right ventricular (RV) branch showed the ST-segment elevation in precordial leads V1-V3 as well. CASE SUMMARY: We reported a patient complaining of acute chest pain and suffering ventricular fibrillation (VF) on admission. The electrocardiogram (ECG) showed mild ST-segment elevation in precordial leads V1-V3 and V4R. Bedside echocardiography displayed normal left ventricular ejection fraction and slight RV dilation. Proximal occlusion of nondominant RCA was confirmed by coronary angiography and urgent percutaneous coronary intervention (PCI) to RCA successfully resolved the chest pain and ST-segment elevation. CONCLUSION: Undoubtedly, coronary angiography is usually the definite measurement for the diagnosis of culprit lesion. However, bedside echocardiography, ST-segment features in left and right precordial leads, and heart rate will be the additional information for judging ST-segment elevation in precordial leads V1-V3 resulting from occlusion of RCA or LAD.


Assuntos
Oclusão Coronária/diagnóstico , Vasos Coronários/diagnóstico por imagem , Eletrocardiografia , Intervenção Coronária Percutânea/métodos , Angiografia Coronária , Oclusão Coronária/fisiopatologia , Oclusão Coronária/cirurgia , Vasos Coronários/cirurgia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico
17.
J Huazhong Univ Sci Technolog Med Sci ; 32(3): 383-388, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22684562

RESUMO

Over-expression of CD151 was found to be associated with metastasis and poor prognosis of prostatic carcinoma. This study was designed to examine the mechanism by which CD151 promotes the proliferation and migration of prostatic cancer cells. The pAAV-CD151, pAAV-GFP and pAAV-CD151-AAA mutant plasmids were constructed and used to transiently transfect PC3 cells (a prostatic carcinoma 3 cell line) by the mediation of Fugene HD. Then, the cells were assigned to control group, pAAV-GFP group, pAAV-CD151 group, and pAAV-CD151-AAA group respectively. Cell proliferation was evaluated by using the 3-[4,5-dimet-hylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method. Cell migration assay was performed by using Boyden chambers. The formation of CD151-integrin α3/α6 complex was determined by the method of co-immunoprecipitation. The protein expression levels of CD151 and extracellular signal-regulated kinase (ERK) were measured by Western blotting. The results showed that transfection of pAAV-CD151 or pAAV-CD151-AAA mutant increased the expression of CD151 protein in PC3 cells. Co-immunoprecipitation showed that more CD151-integrin α3/α6 complex was formed in the pAAV-CD151 group than in the control group, the pAAV-GFP group and the pAAV-CD151-AAA mutant group. Furthermore, the proliferative and migrating capacity of PC3 cells was substantially increased in the pAAV-CD151 group but inhibited in the pAAV-CD151-AAA mutant group. CD151 transfection increased the expression of phospho-ERK. Taken together, it was concluded that CD151 promotes the proliferation and migration of PC3 cells through the formation of CD151-integrin complex and the activation of phosphorylated ERK.


Assuntos
Movimento Celular , Proliferação de Células , Integrina alfa3/metabolismo , Integrina alfa6/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Tetraspanina 24/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino
18.
Acta Pharmacol Sin ; 32(2): 201-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21240296

RESUMO

AIM: The aim of this study was to improve the delivery efficacy and target specificity of the pro-angiogenic gene CD151 to the ischemic heart. METHODS: To achieve the inducible expression of adeno-associated viral (AAV)-delivered CD151 gene in only the ischemic myocardium, we generated an AAV construct in which CD151 expression can be controlled by the hypoxia response element (HRE) sequence from the human Enolase gene. The function of this vector was examined in rat H9C2 cardiac myoblasts and in ischemic rat myocardium. The expression of CD151 in the areas of ischemic myocardium was confirmed at the mRNA level by real-time PCR and on the protein level by Western blot, whereas the CD151 expression in the microvessels within the areas of ischemic myocardium was detected by immunohistochemistry. RESULTS: HRE significantly enhances the expression of CD151 under hypoxic conditions or in the ischemic myocardium, and forced CD151 expression increases the number of microvessels in the ischemic myocardium. CONCLUSION: The AAV-mediated, HRE regulated delivery of the CD151 gene shows higher expression in the ischemic myocardium and more efficiently targets CD151 to the hypoxic regions after myocardial infarction.


Assuntos
Antígenos CD/administração & dosagem , Dependovirus/genética , Vetores Genéticos , Isquemia Miocárdica/terapia , Animais , Antígenos CD/genética , Western Blotting , Modelos Animais de Doenças , Regulação da Expressão Gênica , Terapia Genética/métodos , Humanos , Fator 1 Induzível por Hipóxia/genética , Masculino , Microvasos/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Isquemia Miocárdica/patologia , Fosfopiruvato Hidratase/genética , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley , Tetraspanina 24
19.
Int J Biochem Cell Biol ; 43(4): 642-50, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21237282

RESUMO

Tetraspanin CD151 mainly associates with laminin-binding integrins and forms CD151-integrin complex. We previously reported that CD151 could be a potential target for angiogenesis, but the mechanisms involved are still unclear. This study investigated the role of CD151-integrin complex in angiogenesis and the signaling mechanisms involved. Here we showed that CD151 and CD151-AAA mutant were both well expressed at the protein level. CD151 gene transfer promoted angiogenesis and improved skin temperature of the lateral ischemic hindlimb, whereas CD151-AAA mutant abrogated the increase in capillary density and skin temperature. Further, CD151-AAA mutant failed to activate the FAK, ERK, PI3K/Akt/eNOS, and Rac1/Cdc42 signaling pathways. Moreover, CD151-AAA mutant was unavailable to promote bovine aortic endothelial cells (BAECs) proliferation and migration, in contrast to the effects of CD151. The results suggested that formation of CD151-integrin complex was likely to be a prerequisite for CD151-induced angiogenesis and signaling pathways.


Assuntos
Antígenos CD/metabolismo , Integrina alfa3/metabolismo , Integrina alfa6/metabolismo , Neovascularização Fisiológica , Animais , Antígenos CD/genética , Sequência de Bases , Capilares/metabolismo , Bovinos , Ciclo Celular , Movimento Celular , Proliferação de Células , Dependovirus/genética , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Espaço Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , Mutação , Ligação Proteica , Ratos , Ratos Wistar , Transdução de Sinais , Temperatura Cutânea , Tetraspanina 24 , Cicatrização
20.
J Huazhong Univ Sci Technolog Med Sci ; 30(5): 569-74, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21063836

RESUMO

This study examined the effect of integrin cytoplasmic domain-associated protein 1α (ICAP-1α) and its mutatants T38A and I138A on the adhesion, migration and tube formation of 2H-11 cells. rAAV-ICAP-1α, rAAV-T38A and rAAV-I138A were constructed. After infection, the expression of ICAP-1α and p-ERK1/2, p-c-Jun protein was measured by Western blotting. Adhesion ability was evaluated by using MTT. Cell migration was determined by using Boyden chamber method. Tube formation test was conducted on Matrigel. The results showed that in ICAP-1α, T38A and I138A groups, ICAP-1α protein expression was increased. In T38A and I138A groups, phospho-ERK1/2, phospho-c-Jun protein expressions were significantly increased as compared with the control group and the GFP group. ICAP-1α group protein expression was obviously decreased when compared with the control group and the GFP group. Cell adhesion ratio was 0.1429±0.0080 in control group, 0.1434±0.0077 in GFP group and the ratio in T38A and I138A groups increased to 0.3210±0.0082 and 0.3250±0.0079, respectively. In ICAP-1α group, the ratio was decreased to 0.1005±0.0073. In T38A and I138A groups, the number of migrating 2H-11 cells was increased to 31.45±3.20 and 33.10±5.40 against 18.51±2.80 in control group and 20.47±3.12 in GFP group. In ICAP-1α group, the number was decreased to 12.06±1.72. The number of tube-like structures was increased to 20.41±2.54 in T38A and to 22.26±3.07 in I138A groups as compared to those of control group 12.45±1.84 and GFP group 13.63±2.71. In ICAP-1α group, the number of tube-like structures was decreased to 8.32±1.24. It was suggested that rAAV-T38A and rAAV-I138A transfection can substantially increase 2H-11 cell adhesion, migration and angiogenisis, while rAAV-ICAP-1α can greatly inhibit the effect. These effects might be correlated with ERK1/2 and c-Jun protein phosphorylation.


Assuntos
Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas de Membrana/biossíntese , Proteínas Mutantes/biossíntese , Transfecção , Proteínas Adaptadoras de Transdução de Sinal , Linhagem Celular , Dependovirus/genética , Dependovirus/metabolismo , Células Endoteliais/citologia , Fibronectinas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Proteínas Mutantes/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética
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