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1.
Artigo em Inglês | MEDLINE | ID: mdl-34948554

RESUMO

The Ecological Functional Zone of the Upper Yellow River (EFZUYR) is a critical water-catching area in the Yellow River Basin, the ecological security of which affects the sound development of the ecosystem in the entire basin. Recently, significant land use changes have aggravated regional ecological risks and seriously affected the sustainable development of EFZUYR. In this context, this paper provides an in-depth study of the ecological risks caused by land use landscape changes. With the help of land use data and dynamic degree analysis, the land use transfer matrix, and the landscape pattern index, this paper quantifies the distribution trends of land use landscape patterns in EFZUYR from 1990 to 2018. In addition, this research explores the temporal and spatial dynamic distribution characteristics of landscape ecological risks in this functional zone. The research results show the following: (1) The transfer of land use in EFZUYR from 1990 to 2018 mainly occurred among cultivated land, grassland, and woodland, with the transferred area accounting for 87.16% of the total changed area. (2) The fragmentation degree of built-up areas is 0.1097, 0.1053, 0.0811 and 0.0762 in 1990, 2000, 2010 and 2018, respectively, with a decreasing trend. The dominance degree of grassland has been maintained at the highest level for a long time, with all values above 0.59. The separation degree and the interference degree of built-up areas were the highest and the values of the four periods were above 1.2 and 0.44, respectively. The loss degree of water was the highest, with a value above 0.67, while the value of other land use was mostly below 0.4. (3) The landscape ecological risk of EFZUYR presented a fluctuating rising, falling, and then rising trend. The spatial distribution characteristic of EFZUYR presented "high in the north and south, low in the middle.", which has been maintained for a long time. The proportion of low-risk areas is as high as 70%, and the overall ecological risk of the region was low. However, the ecological risk of some areas, such as Linxia City and Magu County, increased. These findings can provide theoretical support for land use planning and achieving sustainable development of EFZUYR.


Assuntos
Ecossistema , Rios , China , Conservação dos Recursos Naturais , Florestas
2.
Diabetes Res Clin Pract ; 179: 109005, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34391828

RESUMO

AIMS: Intensive glycemic therapy could lead to increased mortality in patients with type 2 diabetes mellitus (T2DM). But it remains unclear whether statins use improves prognosis in T2DM patients with intensive glycemic therapy. METHODS: Using data from Action to Control Cardiovascular Risk in Diabetes trial and performing propensity score matching and Cox proportional hazards regression, we explored the relationship between statin use and the risk of mortality in intensive-therapy group. RESULTS: In the intensive-therapy group, total mortality (TM) in patients with statins treatment is lower than those without statins (hazard ratio (HR), 0.68; 95% confidence interval (CI) 0.49-0.95; P = 0.022); the effects of statins on cardiovascular mortality (CM) and primary outcomes (PO), however, were negligible (CM: HR 0.96; 95% CI 0.61-1.51; P = 0.854; PO: HR 0.88; 95% CI 0.65-1.19; P = 0.415). Besides, the risk of TM, CM and PO in patients with the intensive therapy combined with statins use was similar to those in the standard group (TM: P = 0.445; CM: P = 0.362; PO: P = 0.637). CONCLUSIONS: Statins may alleviate the risk of TM in T2DM patients receiving intensive glycemic therapy.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores de Risco , Resultado do Tratamento
4.
Sci Adv ; 7(13)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33762342

RESUMO

The weak interlamellar interaction of covalent organic framework (COF) nanocrystals inhibit the construction of highly efficient ion/molecular sieving membranes owing to the inferior contaminant selectivity induced by defects in stacked COF membranes and stability issues. Here, a facile in situ molecularly soldered strategy was developed to fabricate defect-free ultrathin COF membranes with precise sieving abilities using the typical chemical environment for COF condensation polymerization and dopamine self-polymerization. The experimental data and density functional theory simulations proved that the reactive oxygen species generated during dopamine polymerization catalyze the nucleophilic reactions of the COF, thus facilitating the counter-diffusion growth of thin COF layers. Notably, dopamine can eliminate the defects in the stacked COF by soldering the COF crystals, fortifying the mechanical properties of the ultrathin COF membranes. The COF membranes exhibited ultrafast precision sieving for molecular separation and ion removal in both aqueous and organic solvents, which surpasses that of state-of-the-art membranes.

5.
Macromol Rapid Commun ; 42(2): e2000481, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33047435

RESUMO

This work reports on the transition of a polyamide ultrathick wall microtubes to microvesicles through self-assembly. An amphiphilic polyamide is synthesized first by the solution polycondensation of sodium isophthalate-5-sulfonate (SIPA) and poly(propylene glycol) bis(2-aminopropyl ether) 2000. Then, its self-assembly in aqueous solution is investigated through direct hydration. The size and morphology of the self-assemblies is investigated by transmission electron microscope (TEM), scanning electron microscope (SEM), atomic force microscope (AFM), and optical microscope (OM) measurements. The result shows that the as-prepared polyamide first self-assembles to thick walled tubes, then these tubes can gradually evolve to ultrathick wall microvesicles with an unusually thick membrane above 330 nm. Both the transition pathway and the mechanism are investigated in micromicroscopy. Most importantly, the microvesicles show great thermal and chemical stability. The novel superstable self-assembly structures as well as the transition mechanism presented here offer a promising perspective for the application in the scope of the biological membrane movements and nanoelectromechanics in medical devices.


Assuntos
Nylons
6.
J Colloid Interface Sci ; 585: 420-432, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33268058

RESUMO

HYPOTHESIS: Flexible and wearable hydrogel strain sensors have attracted significant attention for human activity monitoring and electronic skins. However, it remains a great challenge to develop an integrated hydrogel strain sensor showing intrinsic adhesive performances, tunable mechanical and high strain-sensitive properties. Marine mussels show a superior capacity to adhere to various substrates (including organic and inorganic), while polycaprolactone (PCL) can be easily modified into crosslinkers with different degrees of functionality (bi-, tri-, and quadri-functional groups) to control the crosslinking density. Therefore, the developed mussel-inspired 3,4-dihydroxyphenyl-l-alanine acrylamide-polycaprolactone (l-DMA-PCL) hydrogels could address these issues and serve as the potential wearable strain sensors for biomaterials and healthcare monitoring. EXPERIMENTS: l-DMA monomers were successfully crosslinked by functionalized PCL (bi-, tri-, and quadri-functional) using UV light (wavelength ~ 365 nm) to prepare the l-DMA-PCL hydrogel. Adhesive behaviors, tunable mechanical properties and strain sensing performances of the l-DMA-PCL hydrogels were systematically studied. FINDINGS: The l-DMA-PCL hydrogel exhibited reversible adhesion to various material substrates (including steel, aluminum, ceramics, poly(ethylene terephthalate) (PET), wood, rubber, even for polypropylene (PP) and polytetrafluoroethylene (PTFE)) as well as skin. Moreover, the mechanical properties (stress: 50.2-72.4 KPa, strain: 700-1140%, Young's modulus: 8.6-14.8 KPa, and toughness: 16.4-53.6 KJ/m3) of the hydrogels could be readily tuned by the modulation of functionality degree (bi-, tri-, and quadri-functional) of PCL. Intriguingly, the hydrogel-based wearable strain sensor showing high conductivity (0.0550 S/cm) and sensitive responses to both large (e.g., joint bending) and subtle human motions (e.g., frowning and speaking). Based on these achievements, this work provides new insights into the development of hydrogel with adhesiveness, controllable mechanical performance and high strain sensitivity as a flexible and wearable hydrogel strain sensors.


Assuntos
Hidrogéis , Dispositivos Eletrônicos Vestíveis , Adesivos , Condutividade Elétrica , Humanos , Movimento (Física)
7.
Front Cardiovasc Med ; 8: 777757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004892

RESUMO

Aortic dissection (AD), a dangerous disease threatening to human beings, has a hidden onset and rapid progression and has few effective methods in its early diagnosis. At present, although CT angiography acts as the gold standard on AD diagnosis, it is so expensive and time-consuming that it can hardly offer practical help to patients. Meanwhile, the artificial intelligence technology may provide a cheap but effective approach to building an auxiliary diagnosis model for improving the early AD diagnosis rate by taking advantage of the data of the general conditions of AD patients, such as the data about the basic inspection information. Therefore, this study proposes to hybrid five types of machine learning operators into an integrated diagnosis model, as an auxiliary diagnostic approach, to cooperate with the AD-clinical analysis. To improve the diagnose accuracy, the participating rate of each operator in the proposed model may adjust adaptively according to the result of the data learning. After a set of experimental evaluations, the proposed model, acting as the preliminary AD-discriminant, has reached an accuracy of over 80%, which provides a promising instance for medical colleagues.

8.
Ying Yong Sheng Tai Xue Bao ; 31(10): 3499-3508, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33314840

RESUMO

Wetlands are one of the most productive ecosystems in the world, with functions of water purification, climate regulation, and carbon sinks. Due to the stresses caused by human social development and changes of natural conditions, wetlands have been seriously damaged. We examined the evolutionary law of landscape pattern of wetland along the Yellow River, and acquainted the current situation of wetland resources and dynamic change. Based on satellite images of year 2000, 2009, and 2018 from Landsat, we used landscape indices and geographic detectors to quantitatively analyze the characteristics and driving forces of wetland landscape pattern evolution of the city belt along the Yellow River in Ningxia from 2000 to 2018. The results showed that the wetland area of the city belt along the Yellow River in Ningxia enlarged first and then decreased from 2000 to 2018. The wetland area increased by 52.2 km2 in the early stage of the study with an increasing rate of 8.2%, and decreased by 26.8 km2 with a reduction rate of 3.9% in the later stage. The wetland was mainly transformed to construction land and unused land, with transfer out area being 166.7 and 158.4 km2 respectively. New wetland was mainly transformed from unused land, forest, and grassland, with an area of 543.1 km2. The fragmentation degree of wetland landscape in city belt was increasing, the balanced distribution of all kinds of wetlands was gradually strengthened, the landscape diversity was increasing, and the dominant landscape types were gradually weakening. Natural factors and socio-economic factors jointly affected the evolution of wetland landscape pattern in city belt. Among all socio-economic factors population was the most important one. Among natural factors, precipitation and temperature were important. Other driving factors were relatively weak, but could not be ignored.


Assuntos
Rios , Áreas Alagadas , China , Cidades , Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , Humanos
9.
Polymers (Basel) ; 12(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143107

RESUMO

In order to investigate an influence of the B:Zn:H2O molar ratio on the fire protection efficiency of poly(vinyl acetate)-based thermoplastic intumescent coating materials (ICs), systems containing ammonium polyphosphate, melamine, pentaerythritol and different types of zinc borates (ZBs) were tested in a vertical position in quasi-real fire conditions. 3ZnO·2B2O3·6H2O (ZB6), 2ZnO·3B2O3·3.5H2O (ZB3.5) or 3ZnO·2B2O3 (ZB0) were added in amounts of 1-10 wt. parts/100 wt. parts of the other coating components mixture. Char formation processes and thermal insulation features were investigated using an open-flame furnace heated according to the cellulosic fire curve. Thermogravimetric features (DTG), chemical structures (FTIR) and mechanical strength of the ICs and the chars were analyzed as well. It was revealed that the type and dose of the ZBs significantly affect thermal insulation time (TIT) (up to 450 °C of a steel substrate) and sagging (SI) of the fire-heated coatings as well as the compressive strength of the created chars. The highest TIT value (+89%) was noted for the sample with 2.5 wt. parts of ZB3.5 while the lowest SI (-65%) was observed for the coatings containing 10 wt. parts of the hydrated borates (i.e., ZB3.5 or ZB6). The best mechanical strength was registered for the sample filled with the anhydrous modifier (3 wt. parts of ZB0). The presented results show that the ICs with the proper ZBs can be used for effective fire protection of vertically positioned steel elements.

10.
Aging Med (Milton) ; 3(3): 169-177, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33103037

RESUMO

Coronary heart diseases are tightly associated with aging. Although current revascularization therapies, such as percutaneous coronary interventions (PCI) and coronary artery bypass graft (CABG), improve the clinical outcomes of patients with coronary diseases, their application and therapeutic effects are limited in elderly patients. Thus, developing novel therapeutic strategies, like prompting collateral development or the process of arteriogenesis, is necessary for the treatment of the elderly with coronary diseases. Arteriogenesis (ie, the vascular remodeling from pre-existent arterioles to collateral conductance networks) functions as an essential compensation for tissue hypoperfusion caused by artery occlusion or stenosis, and its mechanisms remain to be elucidated. In this review, we will summarize the roles of the major hydromechanical components in laminar conditions in arteriogenesis, and discuss the potential effects of disturbed flow components in non-laminar conditions.

11.
Chem Commun (Camb) ; 56(17): 2650-2653, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32021995

RESUMO

This work reports on the preparation of giant tubes with millimeter-scale length, micron diameter and ultrathick walls above 250 nm, from the aqueous self-assembly of a novel amphiphilic polyamide. Most interestingly, the tubes display great chemical and thermal stability.

13.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3544-3552, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621242

RESUMO

Located in the hinterland of the Qinghai-Tibet Plateau, Tibet has very limited space sui-table for human living. The spatial distribution of settlements in Tibet is restricted by multiple factors. To reveal the spatial distribution characteristics and explore the main influencing factors of settlements in Tibet, we extracted patch data from the high-resolution images of urban and rural settlements in Tibet based on visual interpretation. Methods such as the kernel density analysis, space hotspot detection, Geodetector and others were applied to analyze the spatial differentiation characteristics and influencing factors, with the aim to provide reference for future settlements selection and formulation of relevant policies on regional economic development in the plateau region. The results showed that urban and rural settlements in Tibet had a clustering pattern, with different overall density distribution. Lhasa was a high-density core, and Ngari Prefecture, Qamdo, and Nyingchi were the "core-edge" structures with low-density edges. The settlement density of Lhasa was as high as 220 ind·km-2, while that of Ngari Prefecture, Qamdo and Nyingchi was only 5.7 ind·km-2. The gap between the two regions was more than 43 times. The clustering of high and low value clusters in urban and rural settlements was remarkable. The number of high-value of large plaques was rare, and the number of low-values of small plaques was dominant. The area of high-value cluster accounted for only 3.7%, concentrated in Lhasa and Lhoka. The proportion of low value cluster area reached 67.2%, mainly distributed in Ngari Prefecture and Nagqu on the Qiangtang Plateau. There were six types of urban and rural settlements in Tibet, which formed two circle structures in the "One River and Two Streams" basin and the "Three Rivers" basin. From the inside to the outside, the large plaque-dominated type, medium-density and cluster-like type, high-density and point-scattered type, low-density and point-scattered type and high-altitude and uninhabited type was successively distributed. Lhasa was dominated by medium-density and cluster-like type, accounting for 31%. Lhoka was dominated by low-density and point-scattered type, accounting for 38%. Qamdo was mainly low-density and point-scattered type, accounting for 51%. The Ngari Prefecture, Nagqu and Shigatse were dominated by high-altitude and uninhabited type, and the proportion of the Ngari Prefecture was as high as 64%. The effects of different factors on the spatial distribution of urban and rural settlements in Tibet were distinctly different. The population and GDP were highly decisive for the distribution of urban and rural settlements. In addition, urban settlements showed strong road orientation, while rural settlements were more characterized by river orientation.


Assuntos
Rios , População Rural , China , Humanos , Tibet
14.
ACS Appl Mater Interfaces ; 11(38): 35501-35508, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31482699

RESUMO

Novel multifunctional core-shell nanoparticles (Fe3O4@PSBMA NPs) with magnetic and zwitterionic properties were first synthesized and efficiently incorporated into the poly(vinylidene fluoride) (PVDF) membranes via magnetically controlled surface segregation toward the better water-energy-food nexus. The combination of zwitterionic polymers poly(sulfobetaine methacrylate) (PSBMA) and Fe3O4 particles can improve the compatibility of additives with the PVDF matrix and significantly improve the migration of Fe3O4@PSBMA NPs onto membrane surfaces under magnetic fields during nonsolvent-induced phase separations. The modified membrane with surface-enriched multifunctional zwitterionic NPs had an enhanced water flux (168%, ∼630.5 L m-2 h-1), excellent fouling resistance (∼93.8%), and increased rejection to bovine serum albumin (94.1%). Most importantly, the PVDF/M-Fe3O4@PSBMA membrane had excellent stability under the long-term filtration test for practical water-treatment applications.

15.
BMC Cardiovasc Disord ; 19(1): 204, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438860

RESUMO

BACKGROUND: Several studies on the growth rates of abdominal aortic aneurysm (AAA) in Chinese population have been conducted; however, this issue remains unclear. The aim of this study is to systematically review published data of the AAA growth rates among people in China. METHODS: We conducted a comprehensive search of multiple databases to identify all studies of AAA growth in the Chinese population from inception until June 2017. AAA growth rates were combined to yield the growth rates at specified aneurysm diameter ranges, with using a random-effects model or fixed-effects model according to heterogeneity. RESULTS: A total of 8257 studies were initially identified and only 4 studies were eventually included. A random-effects analysis showed that the growth rates of AAA in Chinses population is ranging from 0.18 cm/year to 0.75 cm/year. The pooled mean growth rates among individuals with aneurysm measuring 3.0-3.9 cm, 4.0-5.9 cm and ≧ 6.0 cm in diameter were 0.21 cm/year (95% CI: 0.19 cm/year to 0.23 cm/year), 0.38 cm/year (95% CI: 0.33 cm/year to 0.43 cm/year), and 0.71 cm/year (95% CI: 0.64 cm/year to 0.77 cm/year) respectively. Further analysis found that the pooled mean growth rates for individuals with small AAA (diameters measuring 3.0-4.9 cm) was 0.28 cm/year (95% CI: - 0.06 cm/year to 0.61 cm/year)`and for individuals with large AAA (diameters ≥5.0 cm) was 0.75 cm/year (95% CI: 0.20 cm/year to 1.3 cm/year). Finally, meta-regression showed a strong trend of linear relationship between AAA growth rate and aneurysm diameter. CONCLUSIONS: The growth rates of AAA in the Chinese population increase with AAA enlargement and appear to range from 0.18 cm/year in the smallest AAAs to 0.75 cm/year when the diameter exceeds 6 cm. However, based on current studies, it is difficult to estimate the accurate average AAA growth rate in Chinese patients. More large-scale, high-quality studies are required to achieve that. Overall, AAA growth rate increase with increased aneurysm diameter.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia , Angiografia por Tomografia Computadorizada , Ultrassonografia , Aneurisma da Aorta Abdominal/epidemiologia , China/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Tempo
16.
Science ; 363(6431): 1085-1088, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30705153

RESUMO

Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.


Assuntos
Colesterol/biossíntese , Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Hipercolesterolemia/metabolismo , Animais , Anticolesterolemiantes/farmacologia , Atorvastatina/farmacologia , Sequência de Bases , Imunoprecipitação da Cromatina , Doença da Artéria Coronariana/metabolismo , Regulação da Expressão Gênica , Hematopoese/genética , Racemases e Epimerases/metabolismo , Receptores Notch/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
17.
Aging Med (Milton) ; 2(1): 50-55, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31942512

RESUMO

Collateralization is an important way for patients with coronary heart disease to supply blood flow to the ischemic area. At present, research on the mechanism of collateral circulation mainly focuses on the inflammatory response. Monocytes are the kernel of inflammatory response during arteriogenesis. Therefore, we reviewed the recent developments in this field in terms of the dynamic changes of monocytes during collateralization. We searched and scanned PubMed for the following terms until November 2018: collateral, collateralization, monocyte, macrophage, and arteriogenesis. Articles were obtained and examined to figure out the dynamics of monocytes in the progress of collateralization. Substantial research shows that recruitment, infiltration, and phenotypic transformation of monocytes can affect function in various ways, respectively. Mechanical or chemical factors that can produce effects on collateral development may be due partly to impact on dynamics of monocytes. Although mechanisms of dynamics of monocytes during arteriogenesis are not elucidated clearly, there is no doubt that deeper exploration of the underlying mechanisms will contribute to pharmaceutical development aiming for promoting collateral development.

18.
Clin Pharmacol Ther ; 105(1): 201-209, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672839

RESUMO

Development of nitrate tolerance is a major drawback to nitrate therapy. Prostacyclin (PGI2) is a powerful vasodilator produced from prostaglandin (PGH2) by prostacyclin synthase (PGIS) in endothelial cells. This study aimed to determine the role of PGIS S-nitrosylation in nitrate tolerance induced by nitroglycerin (GTN). In endothelial cells, GTN increased PGIS S-nitrosylation and disturbed PGH2 metabolism, which were normalized by mutants of PGIS cysteine 231/441 to alanine (C231/441A). Clearance of nitric oxide by carboxy-PTIO or inhibition of S-nitrosylation by N-acetyl-cysteine decreased GTN-induced PGIS S-nitrosylation. Enforced expression of mutated PGIS with C231/441A markedly abolished GTN-induced PGIS S-nitrosylation and nitrate cross-tolerance in Apoe-/- mice. Inhibition of cyclooxygenase 1 by aspirin, supplementation of PGI2 by beraprost, and inhibition of PGIS S-nitrosylation by N-acetyl-cysteine improved GTN-induced nitrate cross-tolerance in rats. In patients, increased PGIS S-nitrosylation was associated with nitrate tolerance. In conclusion, GTN induces nitrate cross-tolerance through PGIS S-nitrosylation at cysteine 231/441.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Tolerância a Medicamentos/fisiologia , Oxirredutases Intramoleculares/metabolismo , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitroglicerina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Animais , Bovinos , Cricetinae , Sistema Enzimático do Citocromo P-450/genética , Relação Dose-Resposta a Droga , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Oxirredutases Intramoleculares/genética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Vasodilatadores/farmacologia
19.
J Cell Mol Med ; 23(2): 1164-1173, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30450725

RESUMO

Angiogenesis is critical for re-establishing the blood supply to the surviving myocardium after myocardial infarction (MI) in patients with acute coronary syndrome (ACS). MicroRNAs are recognised as important epigenetic regulators of endothelial function. The aim of this study was to determine the roles of microRNAs in angiogenesis. Eighteen circulating microRNAs including miR-185-5p were differently expressed in plasma from patients with ACS by high-throughput RNA sequencing. The expressional levels of miR-185-5p were dramatically reduced in hearts isolated from mice following MI and cultured human umbilical vein endothelial cells (HUVECs) under hypoxia, as determined by fluorescence in situ hybridisation and quantitative RT-PCR. Evidence from computational prediction and luciferase reporter gene activity indicated that cathepsin K (CatK) mRNA is a target of miR-185-5p. In HUVECs, miR-185-5p mimics inhibited cell proliferations, migrations and tube formations under hypoxia, while miR-185-5p inhibitors performed the opposites. Further, the inhibitory effects of miR-185-5p up-regulation on cellular functions of HUVECs were abolished by CatK gene overexpression, and adenovirus-mediated CatK gene silencing ablated these enhancive effects in HUVECs under hypoxia. In vivo studies indicated that gain-function of miR-185-5p by agomir infusion down-regulated CatK gene expression, impaired angiogenesis and delayed the recovery of cardiac functions in mice following MI. These actions of miR-185-5p agonists were mirrored by in vivo knockdown of CatK in mice with MI. Endogenous reductions of miR-185-5p in endothelial cells induced by hypoxia increase CatK gene expression to promote angiogenesis and to accelerate the recovery of cardiac function in mice following MI.


Assuntos
Catepsina K/genética , MicroRNAs/genética , Infarto do Miocárdio/genética , Recuperação de Função Fisiológica/genética , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/patologia , Animais , Linhagem Celular , Proliferação de Células/genética , Regulação para Baixo/genética , Células Endoteliais/patologia , Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipóxia/genética , Camundongos , Miocárdio/patologia , Miócitos Cardíacos/patologia , RNA Mensageiro/genética , Regulação para Cima/genética
20.
J Cell Mol Med ; 22(11): 5208-5219, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30589494

RESUMO

Acute myocardial infarction (MI) is a leading cause of morbidity and mortality in the world. Traditional method to induce MI by left coronary artery (LCA) ligation is typically performed by an invasive approach that requires ventilation and thoracotomy, causing serious injuries in animals undergoing this surgery. We attempted to develop a minimally invasive method (MIM) to induce MI in mice. Under the guide of ultrasound, LCA ligation was performed in mice without ventilation and chest-opening. Compared to sham mice, MIM induced MI in mice as determined by triphenyltetrazolium chloride staining and Masson staining. Mice with MIM surgery revealed the reductions of LVEF, LVFS, E/A and ascending aorta (AAO) blood flow, and the elevations of S-T segment and serum cTn-I levels at 24 post-operative hours. The effects of MI induced by MIM were comparable to the effects of MI produced by traditional method in mice. Importantly, MIM increased the survival rates and caused less inflammation after the surgery of LCA ligation, compared to the surgery of traditional method. Further, MIM induced angiogenesis and apoptosis in ischaemic hearts from mice at postoperative 28 days as similarly as traditional method did. Finally, the MIM model was able to develop into the myocardial ischaemia/reperfusion model by using a balloon catheter with minor modifications. The MI model is able to be efficiently induced by a minimally invasive approach in mice without ventilation and chest-opening. This new model is potentially to be used in studying ischaemia-related heart diseases.


Assuntos
Vasos Coronários/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Infarto do Miocárdio/cirurgia , Isquemia Miocárdica/cirurgia , Animais , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Humanos , Ligadura/métodos , Camundongos , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Miocárdio/patologia , Toracotomia/métodos
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