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1.
Environ Res ; 214(Pt 4): 113975, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35995228

RESUMO

Self-healing concrete is an innovative construction material designed to repair its cracks autogenously or autonomously. The self-healing effect reduces the need for maintenance and increases the longevity of concrete structures, bringing environmental and economic benefits. However, the developed methods to improve self-healing performance, e.g., incorporating advanced techniques or expensive chemical healing agents, significantly increase the cost of concrete manufacture. There is worldwide interest in using waste materials to reduce the cost of self-healing concrete, and a significant amount of studies have been performed on this topic. A review of research on waste-derived self-healing concrete is presented in this paper. The wastes were used in both autogenous and autonomous self-healing approaches, such as mineral admixture, bacteria-based technology, and engineered cementitious composite; different environmental conditions may significantly influence self-healing efficiency due to different reaction mechanisms. In general, waste materials could be reused to manufacture self-healing concrete if adopting appropriate mix design and treatment methods. Self-healing concrete made with various industrial wastes is an efficient way to reduce the manufacturing cost and promote its application in practice.


Assuntos
Resíduos Industriais , Reciclagem , Carbonato de Cálcio , Materiais de Construção , Resíduos
2.
J Environ Manage ; 262: 110352, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32250823

RESUMO

The management of abundant drinking water treatment sludge (DWTS) in landfill remains an important issue. The reuse of DWTS as construction material could contribute to the development of greener concrete product and to mitigating the detrimental environment effect from excessive production of DWTS. This paper investigates the potential of using DWTS as sand replacement in Concrete Paving Blocks (CPB). Five CPB mixtures were designed and the replacement ratios of sand by DWTS were 0%, 5%, 10%, 15%, and 20%, by weight. Properties of CPB such as compressive strength, water absorption, abrasion resistance, sulfate attack and metal leachability were determined. The results indicated that above 10% of DWTS, the replacement was detrimental to such properties of the CPB. Microstructure analysis proved the addition of DWTS could result in ettringite formation and the interfacial transition zone (ITZ) between the cement matrix and DWTS was more porous than that of sand. In addition, the metal leachability test of CPB demonstrated that the addition of high-copper DWTS into CPB was safe.


Assuntos
Água Potável , Purificação da Água , Materiais de Construção , Esgotos , Instalações de Eliminação de Resíduos
3.
Stem Cells ; 36(2): 265-277, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29086457

RESUMO

The ability to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes (CMs) makes them an attractive source for repairing injured myocardium, disease modeling, and drug testing. Although current differentiation protocols yield hPSC-CMs to >90% efficiency, hPSC-CMs exhibit immature characteristics. With the goal of overcoming this limitation, we tested the effects of varying passive stretch on engineered heart muscle (EHM) structural and functional maturation, guided by computational modeling. Human embryonic stem cells (hESCs, H7 line) or human induced pluripotent stem cells (IMR-90 line) were differentiated to hPSC-derived cardiomyocytes (hPSC-CMs) in vitro using a small molecule based protocol. hPSC-CMs were characterized by troponin+ flow cytometry as well as electrophysiological measurements. Afterwards, 1.2 × 106 hPSC-CMs were mixed with 0.4 × 106 human fibroblasts (IMR-90 line) (3:1 ratio) and type-I collagen. The blend was cast into custom-made 12-mm long polydimethylsiloxane reservoirs to vary nominal passive stretch of EHMs to 5, 7, or 9 mm. EHM characteristics were monitored for up to 50 days, with EHMs having a passive stretch of 7 mm giving the most consistent formation. Based on our initial macroscopic observations of EHM formation, we created a computational model that predicts the stress distribution throughout EHMs, which is a function of cellular composition, cellular ratio, and geometry. Based on this predictive modeling, we show cell alignment by immunohistochemistry and coordinated calcium waves by calcium imaging. Furthermore, coordinated calcium waves and mechanical contractions were apparent throughout entire EHMs. The stiffness and active forces of hPSC-derived EHMs are comparable with rat neonatal cardiomyocyte-derived EHMs. Three-dimensional EHMs display increased expression of mature cardiomyocyte genes including sarcomeric protein troponin-T, calcium and potassium ion channels, ß-adrenergic receptors, and t-tubule protein caveolin-3. Passive stretch affects the structural and functional maturation of EHMs. Based on our predictive computational modeling, we show how to optimize cell alignment and calcium dynamics within EHMs. These findings provide a basis for the rational design of EHMs, which enables future scale-up productions for clinical use in cardiovascular tissue engineering. Stem Cells 2018;36:265-277.


Assuntos
Biologia Computacional/métodos , Miocárdio/citologia , Linhagem Celular , Citometria de Fluxo , Humanos , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Engenharia Tecidual/métodos
4.
bioRxiv ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38798547

RESUMO

BACKGROUND: There is growing evidence that pathogenic mutations do not fully explain hypertrophic (HCM) or dilated (DCM) cardiomyopathy phenotypes. We hypothesized that if a patient's genetic background was influencing cardiomyopathy this should be detectable as signatures in gene expression. We built a cardiomyopathy biobank resource for interrogating personalized genotype phenotype relationships in human cell lines. METHODS: We recruited 308 diseased and control patients for our cardiomyopathy stem cell biobank. We successfully reprogrammed PBMCs (peripheral blood mononuclear cells) into induced pluripotent stem cells (iPSCs) for 300 donors. These iPSCs underwent whole genome sequencing and were differentiated into cardiomyocytes for RNA-seq. In addition to annotating pathogenic variants, mutation burden in a panel of cardiomyopathy genes was assessed for correlation with echocardiogram measurements. Line-specific co-expression networks were inferred to evaluate transcriptomic subtypes. Drug treatment targeted the sarcomere, either by activation with omecamtiv mecarbil or inhibition with mavacamten, to alter contractility. RESULTS: We generated an iPSC biobank from 300 donors, which included 101 individuals with HCM and 88 with DCM. Whole genome sequencing of 299 iPSC lines identified 78 unique pathogenic or likely pathogenic mutations in the diseased lines. Notably, only DCM lines lacking a known pathogenic or likely pathogenic mutation replicated a finding in the literature for greater nonsynonymous SNV mutation burden in 102 cardiomyopathy genes to correlate with lower left ventricular ejection fraction in DCM. We analyzed RNA-sequencing data from iPSC-derived cardiomyocytes for 102 donors. Inferred personalized co-expression networks revealed two transcriptional subtypes of HCM. The first subtype exhibited concerted activation of the co-expression network, with the degree of activation reflective of the disease severity of the donor. In contrast, the second HCM subtype and the entire DCM cohort exhibited partial activation of the respective disease network, with the strength of specific gene by gene relationships dependent on the iPSC-derived cardiomyocyte line. ADCY5 was the largest hubnode in both the HCM and DCM networks and partially corrected in response to drug treatment. CONCLUSIONS: We have a established a stem cell biobank for studying cardiomyopathy. Our analysis supports the hypothesis the genetic background influences pathologic gene expression programs and support a role for ADCY5 in cardiomyopathy.

5.
PeerJ Comput Sci ; 9: e1653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077577

RESUMO

The diverse characteristics of heterogeneous data pose challenges in analyzing combined price and volume data. Therefore, appropriately handling heterogeneous financial data is crucial for accurate stock prediction. This article proposes a model that applies customized data processing methods tailored to the characteristics of different types of heterogeneous financial data, enabling finer granularity and improved feature extraction. By utilizing the structured multi-head attention mechanism, the model captures the impact of heterogeneous financial data on stock price trends by extracting data information from technical, financial, and sentiment indicators separately. Experimental results conducted on four representative individual stocks in China's A-share market demonstrate the effectiveness of the proposed method. The model achieves an average MAPE of 1.378%, which is 0.429% lower than the benchmark algorithm. Moreover, the backtesting return rate exhibits an average increase of 28.56%. These results validate that the customized preprocessing method and structured multi-head attention mechanism can enhance prediction accuracy by attending to different types of heterogeneous data individually.

6.
Materials (Basel) ; 16(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36676505

RESUMO

Cement-based sensors include conductive fillers to achieve a sensing capability based on the piezoresistivity phenomenon, in which the electrical resistivity changes with strain. The microstructural characterisation of cement-based sensors can be obtained using a promising non-destructive technique, such as AC impedance spectroscopy (ACIS), which has been recently used by many researchers. This paper reviews the fundamental concepts of piezoresistivity and ACIS in addition to the comparison of equivalent circuit models of cement-based sensors found in the literature. These concepts include piezoresistivity theory, factors affecting piezoresistivity measurement, resistance measurement methodology, strain/damage sensing, causes of piezoresistivity, theories of conduction, AC impedance spectroscopy theory, and the equivalent circuit model. This review aims to provide a comprehensive guide for researchers and practitioners interested in exploring and applying different techniques to self-sensing concrete.

7.
Stem Cell Res ; 72: 103218, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37804546

RESUMO

Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease, with an estimated 500-1000 new cases diagnosed every year. A portion of these cases may be caused by mutations in the BMPR2 gene, suggesting a possible genetic component in the development of the disease. Here, we report two human induced pluripotent stem cell (iPSC) lines generated from IPAH patients. Both cell lines provide valuable insight into the molecular and cellular mechanisms of IPAH and can be used to further understand the disease.


Assuntos
Hipertensão Pulmonar , Células-Tronco Pluripotentes Induzidas , Humanos , Hipertensão Pulmonar/genética , Mutação
8.
Stem Cell Res ; 59: 102657, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34999423

RESUMO

LMNA-related dilated cardiomyopathy (LMNA-DCM) is caused by pathogenic variants in the LMNA gene and is characterized by left ventricular chamber enlargement, reduced systolic function, and arrhythmia. Here, we generated three human induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of three DCM patients carrying the same single heterozygous mutation, c.398 G > A, in LMNA. All lines exhibited normal iPSC morphology, expressed high levels of pluripotency markers, showed normal karyotypes, and could differentiate into the three germ layers. These patient-specific iPSC lines can serve as invaluable tools to model in vitro pathological mechanisms of LMNA-DCM.

9.
Microvasc Res ; 82(2): 105-12, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21554891

RESUMO

P120 catenin (p120ctn) is an adherens junction protein recognized to regulate barrier function, but emerging evidence indicates that p120ctn may also exert control on other cellular functions such as transcriptional suppression of genes. We investigated the hypothesis that loss of p120ctn in human endothelial cells activates transcription of pro-inflammatory adhesion molecules. For study, siRNA targeted to p120ctn was transfected into brain microvascular (HBMECs) or pulmonary artery endothelial cells (HPAECs) for 24-120h, which depleted 50-80% of endogenous p120ctn. This loss of p120ctn resulted in increased promoter reporter activity of transcription factors, NFκB, AP-1, and Kaiso, as well as of target genes, MMP-1 and ICAM-1. Real-time RT-PCR analysis indicated that the mRNA for ICAM-1, VCAM-1, and E- and P-selectins were all upregulated during the period of 24-120h of p120ctn depletion, although the time-course and extent of the expression profiles differed. The upregulated mRNA of adhesion molecules corresponded with increased PMN adhesion to the EC surface and elevated ICAM-1 protein expression. We further explored the role of ERK1/2 as a potential signaling mechanism responsible for regulation of transcriptional activities by p120ctn. Results indicated that loss of p120ctn increased phosphorylated ERK1/2, and a MEK1 inhibitor (PD98059) prevented NFκB nuclear translocation. This implicates ERK1/2 in signaling the NFκB activation induced by p120ctn loss. The findings provide strong evidence that deficiency in p120ctn expression in endothelial cells is a potent stimulus for transcriptional upregulation of multiple adhesion molecules. We conclude that p120ctn functions to suppress transcription, which is an important and novel regulation in vascular endothelium.


Assuntos
Cateninas/fisiologia , Regulação para Cima , Encéfalo/irrigação sanguínea , Cateninas/genética , Linhagem Celular , Células Endoteliais/citologia , Inibidores Enzimáticos/farmacologia , Inativação Gênica , Humanos , Inflamação , Molécula 1 de Adesão Intercelular/metabolismo , Modelos Biológicos , Neutrófilos/citologia , Regiões Promotoras Genéticas , Artéria Pulmonar/citologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Transcrição Gênica , delta Catenina
10.
Asian Pac J Cancer Prev ; 22(3): 705-709, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773532

RESUMO

BACKGROUND: Peripheral neurotoxicity is common in patients with digestive malignancies receiving chemotherapy containing oxaliplatin, and there is still no effective drug to prevent or treat this complication. METHODS: Seventy-nine patients receiving chemotherapy containing oxaliplatin were included, and the relationship between chemotherapy regimens, cycles, and cumulative dose of oxaliplatin and peripheral neurotoxicity was analyzed. Patients were divided into two groups of control or intervention. Twenty-eight patients in the control group received routine chemotherapy care, and 51 patients in the intervention group underwent two-week exercise rehabilitation program. Patients' Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-Ntx), functional tests, and Brief Pain Inventory(BPI) scores as well as interference life scores were assessed before intervention and two weeks after the intervention. RESULTS: In the intervention group, 52.9% patients previously exercised regularly. The FOLFOX regimen was more common in peripheral neurotoxicity (73.4%), and the median oxaliplatin cycles for neurotoxicity was 9 (ranging from 1 to 16). The mean cumulative dose of oxaliplatin was 1080.02 ± 185.22 mg, both the cycles and cumulative dose were positively correlated with the occurrence of peripheral neurotoxicity. Compared with control, the scores of FACT/GOG-Ntx, functional tests, and BPI were significantly decreased in the intervention group (p < 0.05). CONCLUSION: Chemotherapy cycles and cumulative doses were in relation with OIN  , and exercise rehabilitation program could effectively alleviate OIN.
.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias do Sistema Digestório/tratamento farmacológico , Terapia por Exercício/métodos , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/reabilitação , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/efeitos adversos , Humanos , Irinotecano/efeitos adversos , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/reabilitação , Compostos Organoplatínicos/efeitos adversos , Oxaloacetatos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente
11.
Polymers (Basel) ; 13(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34372103

RESUMO

An innovative beam concept made from hollow FRP tube with external flanges and filled with crumbed rubber concrete was investigated with respect to bending and shear. The performance of the rubberised-concrete-filled specimens was then compared with hollow and normal-concrete-filled tubes. A comparison between flanged and non-flanged hollow and concrete-filled tubes was also implemented. Moreover, finite element simulation was conducted to predict the fundamental behaviour of the beams. The results showed that concrete filling slightly improves bending performance but significantly enhances the shear properties of the beam. Adding 25% of crumb rubber in concrete marginally affects the bending and shear performance of the beam when compared with normal-concrete-filled tubes. Moreover, the stiffness-to-FRP weight ratio of a hollow externally flanged round tube is equivalent to that of a concrete-filled non-flanged round tube. The consideration of the pair-based contact surface between an FRP tube and infill concrete in linear finite element modelling predicted the failure loads within a 15% margin of difference.

12.
Stem Cell Res ; 57: 102605, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34856468

RESUMO

SCN5A gene loss-of-function mutations are commonly associated with Brugada syndrome, which represents a risk of lethal arrhythmias and sudden cardiac death. The present report describes the generation of two human induced pluripotent stem cell (iPSC) lines reprogrammed from two Brugada syndrome affected patients carrying SCN5A mutations, c.53506 G>A and c.2102 C>T, respectively. Pluripotency markers, karyotype stability, and differentiation capability into derivatives of the three germ layers were assessed and described in the present report. These lines can be used as a reliable cell model for Brugada syndrome investigations and characterization of leading cellular mechanisms.

13.
Stem Cell Res ; 53: 102279, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33743363

RESUMO

Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that can cause sudden cardiac death and heart failure. HCM often arises from mutations in sarcomeric genes, among which the MYBPC3 is the most frequently mutated. Here we generated two human induced pluripotent stem cell (iPSC) lines from a HCM patient who has a familial history of HCM and his daughter who carries the pathogenic non-coding mutation. All lines show the typical morphology of pluripotent cells, a high expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers. These lines provide a valuable resource for studying the molecular basis of HCM and drug screening for HCM.


Assuntos
Cardiomiopatia Hipertrófica , Células-Tronco Pluripotentes Induzidas , Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica/genética , Heterozigoto , Humanos , Mutação
14.
Gynecol Oncol ; 117(2): 341-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20153884

RESUMO

OBJECTIVE: With the exception of the laying hen, no other animal model of spontaneous ovarian surface epithelial cancer replicates the human disease. Flaxseed is the richest vegetable source of omega-3 fatty acids, which are chemopreventive in breast cancer and may be important in other cancers. The objective of this study was to determine if a flaxseed-enriched diet had a chemopreventive effect on ovarian cancer in the laying hen. METHODS: White Leghorn hens were fed with 10% flaxseed-enriched or standard diet for 1 year. The incidence and severity of ovarian cancer were determined by gross pathology and histology in the two groups. General health markers were also measured. Eggs were collected and analyzed by gas chromatography to determine omega-3 fatty acid levels. RESULTS: A significant reduction in late stage ovarian tumors was detected in the flaxseed-fed hens. Incidence rates of ovarian cancer were not significantly different between the two groups. The results indicate that a flaxseed diet increases overall survival in the laying hen. Flaxseed-fed hens' eggs incorporated significantly more omega-3 fatty acids compared to control hens. CONCLUSIONS: These findings show that 10% flaxseed supplementation for 1 year in the laying hen results in a significant reduction in the severity of ovarian cancer, but no change in the incidence of the disease. Hens fed flaxseed had overall better health and reduced mortality. These findings may provide the basis for a clinical trial that evaluates the efficacy of flaxseed as a chemosuppressant of ovarian cancer in women.


Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Linho , Neoplasias Ovarianas/dietoterapia , Animais , Galinhas , Dieta , Modelos Animais de Doenças , Feminino , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Distribuição Aleatória
15.
Curr Protoc Stem Cell Biol ; 54(1): e114, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32584494

RESUMO

We describe the procedure to isolate genomic DNA, RNA, and protein directly from cryopreserved induced pluripotent stem cell (iPSC) vials using commercially available solid-phase extraction kits, and we report the relationship between macromolecule yields and experimental and storage factors. Sufficient quantities of DNA, RNA, and protein are recoverable from as low as 1 million cryopreserved cells across 728 distinct iPSC lines suitable for whole-genome sequencing, RNA sequencing, and mass spectrometry experiments. Nucleic acids extracted from iPSC stocks cryopreserved up to 4 years maintain sufficient quantity and integrity for downstream analysis with minimal genomic DNA fragmentation. An expected positive correlation exists between cell count and DNA or RNA yield, with comparable yields recovered between cells across different cryostorage timespans. This article provides an effective way to simultaneously isolate iPSC biomolecules for multi-omics investigations. © 2020 Wiley Periodicals LLC. Basic Protocol 1: QIAshredder and AllPrep DNA/RNA/protein mini kit extraction and subsequent DNA quantification and quality analysis Basic Protocol 2: Broad-range RNA quantification and quality assay using QuBit 4 Fluorometer and associated kits.


Assuntos
Criopreservação , DNA/isolamento & purificação , Genômica , Ensaios de Triagem em Larga Escala/métodos , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas/isolamento & purificação , RNA/isolamento & purificação , Fluorometria , Humanos , Modelos Lineares
16.
Materials (Basel) ; 13(17)2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32872478

RESUMO

Concrete wastewater infrastructures are important to modern society but are susceptible to sulfuric acid attack when exposed to an aggressive environment. Fibre-reinforced mortar has been adopted as a promising coating and lining material for degraded reinforced concrete structures due to its unique crack control and excellent anti-corrosion ability. This paper aims to evaluate the performance of polyethylene (PE) fibre-reinforced calcium aluminate cement (CAC)-ground granulated blast furnace slag (GGBFS) blended strain-hardening mortar after sulfuric acid immersion, which represented the aggressive sewer environment. Specimens were exposed to 3% sulfuric acid solution for up to 112 days. Visual, physical and mechanical performance such as water absorption ability, sorptivity, compressive and direct tensile strength were evaluated before and after sulfuric acid attack. In addition, micro-structure changes to the samples after sulfuric acid attack were also assessed by X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) to further understand the deterioration mechanism. The results show that overall fibre-reinforced calcium aluminate cement (CAC)-based samples performed significantly better than fibre-reinforced ordinary Portland cement (OPC)-based samples as well as mortar samples in sulfuric acid solution in regard to visual observations, penetration depth, direct tensile strength and compressive reduction. Gypsum generation in the cementitious matrix of both CAC and OPC-based systems was the main reason behind the deterioration mechanism after acid attack exposure. Moreover, laboratory sulfuric acid testing has been proven for successfully screening the cementitious material against an acidic environment. This method can be considered to design the service life of concrete wastewater pipes.

17.
Sci Total Environ ; 746: 141182, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768782

RESUMO

Drinking water treatment sludge (DWTS) can be recycled into low-strength concrete blocks for construction use. The sodium sulfate resistance and leaching behaviours of the DWTS-derived blocks are investigated in this study. The experimental results show that the addition of DWTS degrades the sodium sulfate resistance of the concrete blocks, however CO2 curing compensates for such property, especially in the case of blocks incorporating 30% DWTS. The improvement can be attributed to the formation of crystalline CaCO3 during CO2 curing for microstructure refinement evidenced by X-ray Computed Tomography and Scanning Electron Microscopy. Leaching analyses show that Cu and Al concentrations increased with increasing DWTS content, and CO2 curing adversely increased the leachability of metals due to the decrease of pH, especially at early leaching stage. Nevertheless, the total leaching concentrations of Cu and Al after 60-day test is far below the prescribed limitations, regardless of samples subject to air curing or CO2 curing. In summary, sludge-derived blocks exposed to CO2 curing are safe and behave well in aggressive environments. Therefore, this study showcases a green technology that successfully recycling DWTS into value-added and durable concrete blocks with low environmental impacts.

18.
Gynecol Oncol ; 113(3): 362-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19321195

RESUMO

OBJECTIVE: Epithelial ovarian carcinoma (EOC) is a leading cause of cancer deaths in women. Until recently, a significant lack of an appropriate animal model has hindered the discovery of early detection markers for ovarian cancer. The aging hen serves as an animal model because it spontaneously develops ovarian adenocarcinomas similar in histological appearance to the human disease. E-cadherin is an adherens protein that is down-regulated in many cancers, but has been shown to be up-regulated in primary human ovarian cancer. Our objective was to evaluate E-cadherin expression in the hen ovary and compare its expression to human ovarian cancer. METHODS: White Leghorn hens aged 185 weeks (cancerous and normal) were used for sample collection. A human ovarian tumor tissue array was used for comparison to the human disease. E-cadherin mRNA and protein expression were analyzed in cancerous and normal hen ovaries by immunohistochemistry (IHC), Western blot, and quantitative real-time PCR (qRT-PCR). Tissue fixed in neutral buffered formalin was used for IHC. Protein from tissue frozen in liquid nitrogen was analyzed by Western blot. RNA was extracted from tissue preserved in RNAlater and analyzed by qRT-PCR. The human ovarian tumor tissue array was used for IHC. RESULTS: E-cadherin mRNA and protein expression were significantly increased in cancerous hen ovaries as compared to ovaries of normal hens by qRT-PCR and Western blot. Similar expression of E-cadherin was observed by IHC in both human and hen ovarian cancer tissues. Similar E-cadherin expression was also observed in primary ovarian tumor and peritoneal metastatic tissue from cancerous hens. CONCLUSIONS: Our findings suggest that the up-regulation of E-cadherin is an early defining event in ovarian cancer and may play a significant role in the initial development of the primary ovarian tumor. E-cadherin also appears to be important in the development of secondary tumors within the peritoneal cavity. Our data suggest that E-cadherin may prove to be an important target in the preventative treatment of metastatic ovarian cancer and further confirm that the laying hen is a good model for the study of human epithelial ovarian carcinoma.


Assuntos
Caderinas/metabolismo , Neoplasias Ovarianas/metabolismo , Regulação para Cima , Animais , Galinhas , Modelos Animais de Doenças , Feminino , Humanos , Ovário/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Gynecol Oncol ; 112(1): 171-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18973935

RESUMO

OBJECTIVES: Ovarian carcinoma is the most lethal gynecological malignancy. The genetic and molecular mechanisms that cause it still remain largely unknown. CYP1B1 is a cytochrome P450 enzyme that catalyzes the conversion of estrogens to genotoxic catechol estrogens which may cause DNA mutations and initiate ovarian epithelial cancer. Our objectives were to evaluate CYP1B1 expression, distribution and localization in the hen ovary and to determine if there is an increased CYP1B1 expression associated with, and possibly involved in the initiation of ovarian cancer. METHODS: Two groups of hens were used: 1. young (50 weeks of age; devoid of cancer) and 2. old (165 weeks of age; divided into two groups: age-matched normal and ovarian cancer). CYP1B1 mRNA and protein expression were analyzed in cancerous ovaries, ovaries of age-matched normal and/or young hens by quantitative real-time PCR (qRT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC). RNA was extracted from tissue preserved in RNAlater for qRT-PCR. Tissue frozen in liquid nitrogen was used for ISH. Tissue fixed in neutral buffered formalin was subjected to IHC. RESULTS: Higher expression of CYP1B1 mRNA was observed in cancerous ovaries as compared to ovaries of young and age-matched normal hens by qRT-PCR. ISH and IHC confirmed that the expression of CYP1B1 was much higher in ovarian tumors compared to ovaries of age-matched normal hens. CYP1B1 mRNA and protein were distributed extensively throughout the carcinoma, while primarily localized to the granulosa layer surrounding the follicle in age-matched normal hens. IHC also showed nuclear localization of CYP1B1. Highly expressed CYP1B1 was found in POF-3 from young and age-matched normal hens as compared to POF-1 and POF-2 by qRT-PCR. No significant difference was found in the expression of CYP1B1 between the distal (site of rupture) and the proximal (site of attachment to the ovary) of POF-1 from young and age-matched normal hens. CONCLUSIONS: High expression of CYP1B1 in the hen ovary is associated with ovarian cancer and our data suggest that CYP1B1 may play an important role in the initiation of ovarian cancer and may prove to be a target for intervention. Moreover, the results of this study further confirm that the laying hen is a good model to study human ovarian cancer.


Assuntos
Hidrocarboneto de Aril Hidroxilases/biossíntese , Neoplasias Ovarianas/enzimologia , Animais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Transformação Celular Neoplásica/metabolismo , Citocromo P-450 CYP1B1 , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Neoplasias Ovarianas/genética , Ovário/enzimologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Sci Rep ; 8(1): 4286, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523826

RESUMO

Despite preliminary confidence on biosafety of polymer coated iron oxide nanoparticles (SPIONs), toxicity concerns have hampered their clinical translation. SPIONs toxicity is known to be due to catalytic activity of their surface and release of toxic Fe ions originating from the core biodegradation, leading to the generation of reactive oxygen species (ROS). Here, we hypothesized that a double-layer polymeric corona comprising of dextran as an interior, and polyethylene glycol (PEG) as an exterior layer better shields the core SPIONs. We found that ROS generation was cell specific and depended on SPIONs concentration, although it was reduced by sufficient PEG immobilization or 100 µM deferoxamine. 24 h following injection, PEGylated samples showed reduction of biodistribution in liver, heterogenous biodistribution profile in spleen, and no influence on NPs blood retention. Sufficient surface masking or administration of deferoxamine could be beneficial strategies in designing and clinical translation of future biomedical SPIONs.


Assuntos
Dextranos/química , Ferro/farmacocinética , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Animais , Células Cultivadas , Coloides/química , Desferroxamina/farmacologia , Liberação Controlada de Fármacos , Feminino , Compostos Férricos/química , Ferro/toxicidade , Quelantes de Ferro/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Nanopartículas Metálicas/efeitos adversos , Camundongos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Distribuição Tecidual
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