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1.
Artigo em Inglês | MEDLINE | ID: mdl-39180571

RESUMO

PURPOSE: This study aims to explore the correlation between PET and CMR in integrated [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging and its value in the diagnosis and risk assessment of hypertrophic cardiomyopathy (HCM). METHODS: This study included 20 HCM patients and 11 age- and gender-matched controls. PET analysis evaluated left ventricular (LV) [68Ga]Ga-FAPI-04 uptake, including SUVmax, TBR, cardiac fibroblast activity (CFA) and volume (CFV), and total SUV of the 16 segments. CMR tissue characterization parameters included cardiac function, myocardial thickness, late gadolinium enhancement (LGE), relaxation time, extracellular volume (ECV), and peak strain parameters. The 5-year sudden cardiac death (SCD) risk score and the 2-year and 5-year atrial fibrillation (AF) risk scores were calculated for each patient. The study analyzed differences between HCM patients and controls, the correlation between [68Ga]Ga-FAPI-04 PET and concurrent CMR imaging results, and the predictive value of PET/CMR. RESULT: The FAPI uptake, myocardial mass, myocardial thickness, and T1/T2 mapping values were significantly higher in HCM patients compared to controls. Twenty HCM patients and their 320 myocardial segments were discussed. Increased [68Ga]Ga-FAPI-04 uptake in the left ventricular wall was observed in 95% (19/20) of the patients, covering 48.8% (156/320) of the segments. On concurrent CMR, 80% (16/20) of the patients showed LGE, including 95 (29.7%) segments. The FAPI(+)LGE(+) segments exhibited the highest myocardial PET uptake, greatest thickness, longest T1/T2 native values, largest ECV value and the greatest loss of myocardial strain capacity (P < 0.05). There was a significant correlation between FAPI uptake and CMR parameters (P < 0.05). Higher [68Ga]Ga-FAPI-04 uptake showed a positive correlation with SCD and AF risk scores (P < 0.05). The number of LGE(+) segments, mapping parameters, and ECV values in CMR also had prognostic significance. Combining PET with CMR aided in further risk stratification of HCM. CONCLUSION: [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging has potential value in the detection of damaged myocardial lesions and risk assessment of HCM patients. [68Ga]Ga-FAPI-04 PET can detect more affected myocardium compared to CMR, and segments with abnormalities in both PET and CMR show more severe myocardial damage.

2.
J Endovasc Ther ; : 15266028241266223, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058244

RESUMO

OBJECTIVE: The study aimed to investigate the early results of directional femoral ultrasound-guided compression technique (UCT) using in percutaneous mechanical thrombectomy (PMT) for acute deep vein thrombosis (DVT). METHODS: Consecutive single-center patients with acute iliofemoral DVT who underwent PMT from January 2020 to December 2021 were included. Directional femoral UCT was used to adjust the PMT catheter into the residual thrombus in the inguinal region by ultrasound compression to improve the thrombus clearance rate. Patients were retrospectively analyzed and divided into 2 groups based on PMT with or without directional femoral UCT. The primary efficacy outcome was the incidence of post-thrombotic syndrome (PTS) at 24-month follow-up. The secondary efficacy outcomes included common femoral venous thrombus removal grade, total thrombus removal grade, venous primary patency rate, and incidence of moderate-to-severe PTS at 24-month follow-up. The safety outcomes included complications, major bleeding events, and death at 24-month follow-up. RESULTS: A total of 96 patients were included in the study: 42 patients underwent PMT with directional femoral UCT and 54 patients underwent PMT without UCT. There was no significant difference in baseline characteristics between the 2 groups. The percentages of patients achieved common femoral venous thrombus removal grade 3 and total thrombus removal grade 3 were significantly higher in the PMT with UCT group than those in the PMT without UCT group (p<0.001). The 24-month primary patency rate was significantly higher in the PMT with UCT group than that in the PMT without UCT group (90.0% vs 71.2%, p=0.027). The incidence of PTS was significantly lower in the PMT with UCT group (10.0%) than that in the PMT without UCT group (28.8%) (p=0.027). CONCLUSION: PMT with directional femoral UCT could improve the thrombus clearance rate and primary patency rate of acute iliofemoral DVT and might decrease the incidence of PTS compared to traditional PMT treatment without UCT. CLINICAL IMPACT: Residual thrombus in common femoral vein is a difficult problem associated with higher incidence of PTS. Few studies have focused on common femoral venous thrombus clearance. PMT with directional femoral UCT could improve the thrombus clearance rate and primary patency rate of acute iliofemoral DVT, and might decrease the incidence of PTS compared to traditional PMT treatment without UCT. Directional femoral UCT is recommended in PMT treatment of acute iliofemoral DVT.

3.
Oncogene ; 43(21): 1631-1643, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38589675

RESUMO

Androgen deprivation therapy (ADT) is the first line of treatment for metastatic prostate cancer (PCa) that effectively delays the tumor progression. However, it also increases the risk of venous thrombosis event (VTE) in patients, a leading cause of mortality. How a pro-thrombotic cascade is induced by ADT remains poorly understood. Here, we report that protein disulfide isomerase A2 (PDIA2) is upregulated in PCa cells to promote VTE formation and enhance PCa cells resistant to ADT. Using various in vitro and in vivo models, we demonstrated a dual function of PDIA2 that enhances tumor-mediated pro-coagulation activity via tumor-derived extracellular vehicles (EVs). It also stimulates PCa cell proliferation, colony formation, and xenograft growth androgen-independently. Mechanistically, PDIA2 activates the tissue factor (TF) on EVs through its isomerase activity, which subsequently triggers a pro-thrombotic cascade in the blood. Additionally, TF-containing EVs can activate the Src kinase inside PCa cells to enhance the AR signaling ligand independently. Androgen deprivation does not alter PDIA2 expression in PCa cells but enhances PDIA2 translocation to the cell membrane and EVs via suppressing the clathrin-dependent endocytic process. Co-recruitment of AR and FOXA1 to the PDIA2 promoter is required for PDIA2 transcription under androgen-deprived conditions. Importantly, blocking PDIA2 isomerase activity suppresses the pro-coagulation activity of patient plasma, PCa cell, and xenograft samples as well as castrate-resistant PCa xenograft growth. These results demonstrate that PDIA2 promotes VTE and tumor progression via activating TF from tumor-derived EVs. They rationalize pharmacological inhibition of PDIA2 to suppress ADT-induced VTE and castrate-resistant tumor progression.


Assuntos
Progressão da Doença , Neoplasias de Próstata Resistentes à Castração , Isomerases de Dissulfetos de Proteínas , Trombose Venosa , Animais , Humanos , Masculino , Camundongos , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/efeitos adversos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Isomerases de Dissulfetos de Proteínas/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Tromboplastina/metabolismo , Tromboplastina/genética , Trombose Venosa/metabolismo , Trombose Venosa/induzido quimicamente , Trombose Venosa/patologia , Trombose Venosa/genética , Trombose Venosa/etiologia , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Endovasc Ther ; : 15266028231159243, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927094

RESUMO

PURPOSE: To evaluate the safety and efficacy of Innospring® stent, a novel self-expanding interwoven nitinol stent, in treating femoropopliteal atherosclerotic lesions. METHODS: A prospective, single-center, single-arm, first-in-human study enrolled 15 patients (mean age 73.1 years; 13 men) to evaluate the safety and efficacy of the Innospring® stent monitored by core laboratories. The inclusion criteria were claudication or ischemic rest pain, de novo lesions or nonstented restenosis, >70% stenosis, lesion length <20 cm, and a reference vessel diameter of 4-7 mm. The primary safety endpoint was 30-day major adverse events. The primary efficacy end point was stent patency at 12 months. Follow-up evaluations were conducted at 30 days, 6 months, and 12 months. RESULTS: The lesion length was 6.1 ± 3.5 mm. Fourteen (93.3%) patients had lesions of the superficial femoral artery and 3 (20.0%) patients had lesions of the popliteal artery. Nine (60.0%) patients had moderate-to-severe calcified lesion. Technical and procedural success was 100%. No patients experienced major adverse events in the first 30 days. The Rutherford category showed significant and sustained improvement at 6 and 12 months. The 12-month follow-up radiographs obtained in 13 patients confirmed the absence of stent fractures in 100% of examinations. The cumulative primary stent patency rate at 6 and 12 months were 93.3% and 84.6%, respectively. CONCLUSION: Stenting of the superficial femoral and popliteal arteries using the Innospring® stent is safe and effective. This competing interwoven nitinol stent may provide superior stent integrity and fracture-resistance as well as serve areas under extreme mechanical stress. CLINICAL IMPACT: Endovascular recanalization is a widely accepted and recommended treatment for symptomatic peripheral artery diseases. The Innospring® stent is a novel self-expanding interwoven stent containing eight nitinol wires with additional radial force, fracture-resistance, and visibility under fluoroscopy. This first-in-human study using the Innospring® stent in patients with femoropopliteal occlusive disease reported that stenting of the superficial femoral and popliteal arteries using the Innospring® stent is safe and effective. This competing interwoven nitinol stent may provide an impressive stent integrity and fracture-resistance as well as serve areas under extreme mechanical stress.

5.
IEEE J Biomed Health Inform ; 27(1): 65-74, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36251916

RESUMO

Hepatocellular carcinoma (HCC) is one of the most critical health problems in the world. For proper treatment, it is important to identify the grade of cancer morbidity from HCC biopsy image. The diagnostic work is not only time-consuming but also subjective. The same biopsy image may be diagnosed as of different grades by different doctors, due to lack of experience or difference in opinion. In this work, we proposed an automatic grading system with classification accuracy matching to an experienced doctor, to help augment the diagnosis process. First, we proposed a segmentation method to isolate all nucleus-like objects present in a biopsy image. Non-target objects (here the target is a single HCC nucleus) present in the biopsy image are isolated too in the segmentation process. To eliminate such non-target objects, we proposed clustering of segmented images and a novel method to filter out target objects. Next, we proposed a two track neural network, where input consists of 2 different images. It combines a single segmented nucleus and a random cropped texture patch of the biopsy image to which the nucleus belongs. At this classifier output, we grade the single nucleus. Finally, a majority voting method is used to identify the grade of the whole biopsy image. We achieved an accuracy of 99.03% for nucleus image grading and 99.66% accuracy for grading biopsy images.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Algoritmos , Neoplasias Hepáticas/patologia , Redes Neurais de Computação , Biópsia , Processamento de Imagem Assistida por Computador/métodos
6.
Thromb Haemost ; 123(1): 97-107, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36462769

RESUMO

Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis. The mRNA expression of the synthetic biomarker Collagen Type I Alpha 1 Chain (COL1A1) gene is upregulated during the switch of VSMCs from the contractile to the synthetic phenotype. The association of noncoding circular RNAs transcribed by the COL1A1 gene with VSMC phenotype alteration and atherogenesis remains unclear. Here we reported a COL1A1 circular RNA (circCOL1A1) which is specifically expressed in VSMCs and is upregulated during phenotype alteration of VSMCs. CircCOL1A1 is also detectable in the serum or plasma. Healthy vascular tissues have a low expression of CircCOL1A1, while it is upregulated in atherosclerosis patients. Through ex vivo and in vitro assays, we found that circCOL1A1 can promote VSMC phenotype switch. Mechanistic analysis showed that circCOL1A1 may exert its function as a competing endogenous RNA of miR-30a-5p. Upregulation of circCOL1A1 ameliorates the inhibitory effect of miR-30a-5p on its target SMAD1, which leads to suppression of transforming growth factor-ß (TGF-ß) signaling. Our findings demonstrate that circCOL1A1 promotes the phenotype switch of VSMCs through the miR-30a-5p/SMAD1/TGF-ß axis and it may serve as a novel marker of atherogenesis or as a therapeutic target for atherosclerosis.


Assuntos
Aterosclerose , MicroRNAs , Humanos , Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Células Cultivadas , MicroRNAs/metabolismo , Músculo Liso Vascular , Miócitos de Músculo Liso/patologia , Fenótipo , RNA Circular/genética , RNA Circular/metabolismo , Fator de Crescimento Transformador beta/metabolismo
7.
Materials (Basel) ; 17(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38204047

RESUMO

Concrete cracking is a significant issue in the global construction industry, and the restraint stress of concrete is a crucial contributing factor to early concrete cracking. The addition of magnesium oxide additive (MEA) to concrete is a method to enhance its crack resistance. In this paper, concrete specimens with four different contents of MEA were tested with a temperature stress testing machine. The deformation characteristics and mechanical properties of concrete with varying contents of MEA were investigated using both free deformation tests and fully constrained deformation tests. The prediction model for the early restrained stress of concrete was developed by integrating the stress relaxation phenomenon of concrete with models for autogenous shrinkage, temperature deformation, and elastic modulus. According to the results, (1) the thermal expansion coefficient exhibits a pattern of initially increasing and subsequently decreasing with the increasing ratio of MEA; (2) the addition of 3% and 8% MEA can offset 23% and 35.1% of the concrete's self-shrinkage, respectively. Nevertheless, when the added MEA content is 5%, the self-shrinkage of concrete increases by 6%; (3) the addition of 3-8% MEA can result in a 0.5-1.67 times increase in the maximum expansion stress of concrete, as well as a 0.5-0.95 times increase in cracking stress; (4) as the MEA content continues to increase, the stress relaxation level of concrete also increases. In comparison to concrete mixed without MEA, the maximum increase in the stress relaxation level of concrete is 65.5%, thereby enhancing the concrete's anti-cracking ability. However, when the MEA dosage reaches a certain threshold, the stress relaxation enhancement brought about by the addition of MEA will no longer be significant; (5) when compared to the experimental data, the established model of early-age constraint stress accurately predicts the tensile constraint stress of concrete.

8.
Medicine (Baltimore) ; 101(39): e30594, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181005

RESUMO

BACKGROUND: Numerous studies have explored whether serum beta 2-microglobulin (ß2-MG) can be used as a biomarker for monitoring systemic lupus erythematosus (SLE) disease activity, but the results are conflicting. Therefore, we performed a systematic meta-analysis to further investigate the correlation between serum ß2-MG level and SLE disease activity. METHODS: PubMed, Web of Science, Embase, and CNKI databases were thoroughly searched for eligible studies through April 2022. Standardized mean differences with 95% confidence intervals (95% CIs) were used to depict the differences in serum ß2-MG levels between groups compared in the studies. The correlation between serum ß2-MG level and SLE disease activity was assessed using Fisher z-values. RESULTS: Sixteen articles with combined 1368 SLE patients were included in this meta-analysis. Serum ß2-MG levels were significantly higher in SLE patients than in healthy controls (pooled standardized mean difference: 3.98, 95% CI: 2.50-5.46, P < .01). In addition, patients with active SLE had an increased serum ß2-MG concentration compared to their inactive SLE counterparts. Furthermore, a positive correlation was observed between serum ß2-MG levels and SLE disease activity (pooled Fisher z = 0.78, 95% CI: 0.61-0.96, P < .01). CONCLUSIONS: This study suggests that patients with SLE have higher serum ß2-MG levels than healthy controls and that serum ß2-MG levels are positively correlated with SLE disease activity. Thus, serum ß2-MG level may be a promising biomarker for monitoring SLE disease activity.


Assuntos
Lúpus Eritematoso Sistêmico , Microglobulina beta-2 , Biomarcadores , Humanos , Cooperação do Paciente
9.
Front Immunol ; 13: 952164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967343

RESUMO

Vascular intimal hyperplasia (VIH) is an important stage of atherosclerosis (AS), in which macrophages not only play a critical role in local inflammation, but also transform into foam cells to participate into plaque formation, where they appear to be heterogeneous. Recently, it was shown that CD11c+ macrophages were more associated with active plaque progression. However, the molecular regulation of phenotypic changes of plaque macrophages during VIH has not been clarified and thus addressed in the current study. Since CD11c- cells were M2a-polarized anti-inflammatory macrophages, while CD11c+ cells were M1/M2b-polarized pro-inflammatory macrophages, we used bioinformatics tools to analyze the CD11c+ versus CD11c- plaque macrophages, aiming to detect the differential genes associated with M1/M2 macrophage polarization. We obtained 122 differential genes that were significantly altered in CD11c+ versus CD11c- plaque macrophages, regardless of CD11b expression. Next, hub genes were predicted in these 122 genes, from which we detected 3 candidates, interleukin 6 (Il6), Decorin (Dcn) and Tissue inhibitor matrix metalloproteinase 1 (Timp1). The effects of these 3 genes on CD11c expression as well as on the macrophage polarization were assessed in vitro, showing that only expression of Il6, but not expression of Dcn or Timp1, induced M1/M2b-like polarization in M2a macrophages. Moreover, only suppression of Il6, but not suppression of either of Dcn or Timp1, induced M2a-like polarization in M1/M2b macrophages. Furthermore, pharmaceutical suppression of Il6 attenuated VIH formation and progression of AS in a mouse model that co-applied apolipoprotein E-knockout and high-fat diet. Together, our data suggest that formation of VIH can be controlled through modulating macrophage polarization, as a promising therapeutic approach for prevent AS.


Assuntos
Aterosclerose , Interleucina-6 , Ativação de Macrófagos , Macrófagos , Placa Aterosclerótica , Túnica Íntima , Animais , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Hiperplasia/genética , Hiperplasia/imunologia , Hiperplasia/patologia , Interleucina-6/genética , Interleucina-6/imunologia , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Placa Aterosclerótica/genética , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Túnica Íntima/imunologia , Túnica Íntima/patologia
10.
Funct Integr Genomics ; 22(5): 951-964, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35678921

RESUMO

Cytoplasmic male sterility (CMS) has been widely used in crop cross breeding. There has been much research on wheat CMS. However, the correlation between S-type CMS and mitochondrial genome remains elusive. Herein, we sequenced the mitochondrial genome of wheat CMS line and compared it with the maintainer line. The results showed that the mitochondrial genome of CMS line encoded 26 tRNAs, 8 rRNAs, and 35 protein-coding genes, and the cob encoding complex III in which the protein coding gene is mutated. This protein is known to affect reactive oxygen (ROS) production. The analysis of ROS metabolism in developing anthers showed that the deficiency of antioxidants and antioxidant enzymes in the sterile system aggravated membrane lipid oxidation, resulting in ROS accumulation, and influencing the anther development. Herein, cob is considered as a candidate causative gene sequence for CMS.


Assuntos
Genoma Mitocondrial , Triticum , Antioxidantes , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica de Plantas , Lipídeos de Membrana , Oxigênio/metabolismo , Melhoramento Vegetal , Infertilidade das Plantas/genética , Espécies Reativas de Oxigênio/metabolismo , Triticum/genética , Triticum/metabolismo
12.
Nat Comput Sci ; 2(7): 451-462, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38177863

RESUMO

Several previously proposed deep learning methods to design amino acid sequences that autonomously fold into a given protein backbone yielded promising results in computational tests but did not outperform conventional energy function-based methods in wet experiments. Here we present the ABACUS-R method, which uses an encoder-decoder network trained using a multitask learning strategy to predict the sidechain type of a central residue from its three-dimensional local environment, which includes, besides other features, the types but not the conformations of the surrounding sidechains. This eliminates the need to reconstruct and optimize sidechain structures, and drastically simplifies the sequence design process. Thus iteratively applying the encoder-decoder to different central residues is able to produce self-consistent overall sequences for a target backbone. Results of wet experiments, including five structures solved by X-ray crystallography, show that ABACUS-R outperforms state-of-the-art energy function-based methods in success rate and design precision.

14.
Cell Prolif ; 54(5): e13023, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33759281

RESUMO

BACKGROUND: Vascular smooth muscle cells (VSMC) switch to macrophage-like cells after cholesterol loading, and this change may play an important role in atherogenesis. Muscleblind-like splicing regulator 1 (MBNL1) is a well-known splicing factor that has been implicated in many cellular processes. However, the role of MBNL1 in VSMC macrophage-like transdifferentiation is largely unknown. In this study, we aim to characterize the role of MBNL1-induced gene splicing during atherogenesis. METHODS: The expression of MBNL1 and Abelson interactor 1 (Abi1) splice variants (Abi1-e10 and Abi1-Δe10) was compared between artery tissues from healthy donors and atherosclerosis patients. Regulatory mechanisms of MBNL1-induced Abi1 gene splicing were studied, and the signal pathways mediated by Abi1 splice variants were investigated in VSMC. RESULTS: Loss of MBNL1 was found in the macrophage-like VSMC (VSMC-M) in artery wall from atherosclerosis patients. In vitro and in vivo evidence confirmed that Abi1 is one of the MBNL1 target genes. Loss of MBNL1 significantly induces the Abi1-Δe10 isoform expression. Compared to the known actin organization activities of the Abi1 gene, we discovered a novel action of Abi1-Δe10, whereby Abi1-Δe10 activates Rac1 independent of upstream stimulation and triggers the Rac1-NOX1-ROS pathway, which results in increased expression of transcription factor Kruppel-like factor 4 (KLF4). While Abi1-Δe10 inhibits contractile VSMC biomarkers expression and cell contraction, it stimulates VSMC proliferation, migration and macrophage-like transdifferentiation. CONCLUSION: Loss-of-function of MBNL1 activates VSMC-M transdifferentiation to promote atherogenesis through regulating Abi1 RNA splicing.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas do Citoesqueleto/genética , Músculo Liso Vascular/metabolismo , Splicing de RNA , Proteínas de Ligação a RNA/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Desdiferenciação Celular , Células Cultivadas , Proteínas do Citoesqueleto/metabolismo , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Músculo Liso Vascular/citologia , NADPH Oxidase 1/antagonistas & inibidores , NADPH Oxidase 1/genética , NADPH Oxidase 1/metabolismo , Fenótipo , Isoformas de Proteínas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismo
15.
Atherosclerosis ; 313: 102-110, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33038663

RESUMO

BACKGROUND AND AIMS: Phenotypic switch of vascular smooth muscle cells (VSMC) plays a key role in the pathogenesis of atherosclerosis and restenosis after artery intervention. Transcription repressor element 1-silencing transcription factor (REST) has been identified as key regulator of VSMC proliferation. In the present study, we sought to investigate the potential association of E3-ubiquitin ligase ß-TRCP mediated REST protein degradation with Kv1.3 expression during VSMC phenotypic switch. METHODS: Protein and mRNA expression was measured in ex vivo and in vitro models. Protein interaction and ubiquitination were analyzed by immunoprecipitation assays. ChIP assays were performed to assess the relationship between REST and targeted DNA binding site. RESULTS: We found that the expression level of E3-ubiquitin ligase ß-TRCP is significantly increased during VSMC phenotypic switch. REST protein ubiquitination mediated by ß-TRCP is critical for VSMC proliferation and migration. We also found that the gene KCNA3 encoding potassium channel protein Kv1.3 contains a functional REST binding site and is repressed by REST. Downregulation of REST by ß-TRCP and consequently upregulation of Kv1.3 are important events during VSMC phenotypic switch. Furthermore, upregulated Kv1.3 accelerates ß-TRCP modulated REST degradation through Erk1/2 signaling. CONCLUSIONS: Our results reveal a fundamental role for regulatory interactions between ß-TRCP modulated REST degradation and Kv1.3 in the control of the multilayered regulatory programs required for VSMC phenotype switch.


Assuntos
Canal de Potássio Kv1.3/metabolismo , Músculo Liso Vascular , Proteínas Repressoras/metabolismo , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Animais , Humanos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fenótipo , Proteólise , Proteínas Contendo Repetições de beta-Transducina/genética
16.
Materials (Basel) ; 9(3)2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28773271

RESUMO

This study comparably assessed the pozzolanic effect of silica fume (SF) and ground rice husk ash (RHA) as supplementary cementing materials on the properties of blended cement pastes and concretes. A commonly commercial silica fume (SF) and locally-produced rice husk ash (RHA) samples with two finenesses (one with larger size than cement and the other with smaller size than cement) were used in this study. Material properties of SF and RHA were experimentally characterized. Hydration and mechanical properties of cement pastes incorporating SF and RHA were determined by thermogravimetric analysis (TGA) and compressive strength tests, respectively. Properties of concretes regarding workability, mechanical property, durability, and microstructure were evaluated. Results showed that, although the finely ground RHA used in this study possessed lower SiO2 content and higher particle size compared to SF, it exhibited comparable pozzolanic reactivity with SF due to the nano-scale pores on its each single particle, leading to a higher specific surface area. The optimal replacement levels of SF and RHA were 10% by weight of cement in pastes and concretes. Although addition of SF and RHA led to a significant reduction in slump for the fresh mixtures, inclusion of up to 30% of SF or 15% of ground RHA did not adversely affect the strength of concretes. At the same mix, incorporation of finely-ground RHA in cement composites provided comparable mechanical properties, hydration degree, and durability with SF blended cement composites, owing to the porous structure and high specific surface area of RHA particles. Microstructure morphology analysis of concretes explored by scanning electron microscopy (SEM) further validated the strength and the durability test results.

17.
Acta Crystallogr E Crystallogr Commun ; 71(Pt 5): m116-7, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25995892

RESUMO

The title compound, [Cu4(C11H13NO4)4]·CH3CH2OH·2.5H2O, is an electronically neutral tetra-nuclear copper(II) complex with a cubane-like Cu4O4 core. The complete molecule has point group symmetry 2. The phenol hy-droxy group and one of the three alcohol hy-droxy groups of each 2-{[tris-(hy-droxy-meth-yl)meth-yl]imino-meth-yl}phenol ligand are depro-ton-ated, while the secondary amine and the other two hy-droxy groups remain unchanged. The Cu(II) atoms in the Cu4O4 core are connected by four µ3-O atoms from the deprotonated alcohol hy-droxy groups. Each of the penta-coordinated Cu(II) ions has an NO4 distorted square-pyramidal environment through coordination to the tridentate Schiff base ligands. The Cu-N/O bond lengths span the range 1.902 (4)-1.955 (4) Å, similar to values reported for related structures. There are O-H⋯O hydrogen-bond inter-actions between the complex molecules and the ethanol and water solvent molecules, leading to the formation of a three-dimensional network. The ethanol solvent molecule is disordered about a twofold rotation axis. One of the two independent water molecules is also located on this twofold rotation axis and shows half-occupancy.

18.
Materials (Basel) ; 8(3): 1089-1107, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-28787990

RESUMO

In order to model the effect of mixture parameters and material properties on the hardened properties of, prestressed self-compacting concrete (SCC), and also to investigate the extensions of the statistical models, a factorial design was employed to identify the relative significance of these primary parameters and their interactions in terms of the mechanical and visco-elastic properties of SCC. In addition to the 16 fractional factorial mixtures evaluated in the modeled region of -1 to +1, eight axial mixtures were prepared at extreme values of -2 and +2 with the other variables maintained at the central points. Four replicate central mixtures were also evaluated. The effects of five mixture parameters, including binder type, binder content, dosage of viscosity-modifying admixture (VMA), water-cementitious material ratio (w/cm), and sand-to-total aggregate ratio (S/A) on compressive strength, modulus of elasticity, as well as autogenous and drying shrinkage are discussed. The applications of the models to better understand trade-offs between mixture parameters and carry out comparisons among various responses are also highlighted. A logical design approach would be to use the existing model to predict the optimal design, and then run selected tests to quantify the influence of the new binder on the model.

19.
Materials (Basel) ; 7(9): 6620-6631, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28788202

RESUMO

Deposition of chloride ions in the surface layer of concrete is investigated in this study. In real concrete structure, chloride ions from the service environment can penetrate into concrete and deposit in the surface layer, to form the boundary condition for further diffusion towards the interior. The deposit amount of chloride ions in the surface layer is normally a function of time, rather than a constant. In the experimental investigation, concrete specimens with different mix proportions are immersed in NaCl solution with a mass concentration of 5%, to simulate the shallow immersion condition in sea water, and the surface chloride concentrations are measured at different ages. It is found that the surface chloride concentration increases following the increasing immersion durations, and varies from a weight percentage of 0.161%-0.781% in concretes with different mix proportions. The w/c (water-to-cement ratio) influences the surface chloride concentration significantly, and the higher the w/c is, the higher the surface chloride concentration will be, at the same age. However, following the prolonging of immersion duration, the difference in surface chloride concentration induced by w/c becomes smaller and smaller. The incorporation of fly ash leads to higher surface chloride concentration. The phenomena are explained based on pore structure analyses.

20.
Opt Express ; 21(4): 4790-5, 2013 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-23482013

RESUMO

The fluorescence enhancement in broadband Cr-doped fibers (CDFs) fabricated by a drawing tower with a redrawn powder-in-tube preform is proposed and demonstrated. The CDFs after heat treatment exhibited Cr4⁺ emission enhancement with spectral density of 200 pW/nm, verified by the formation of α-Mg2SiO4 nanocrystalline structures in the core of CDFs. The high fluorescence achievement in the CDFs is essential to develop a broadband CDF amplifier for next-generation optical communication systems.


Assuntos
Cromo/química , Tecnologia de Fibra Óptica/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Fluorescência
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