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1.
Aging Clin Exp Res ; 36(1): 155, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39085739

RESUMEN

BACKGROUND AND OBJECTIVE: Malnutrition is prevalent among elderly patients with COPD, who also experience a high rate of readmission. Therefore, it is imperative to investigate the nutrition status of these patients, identify risk factors for readmission, and offer insights for clinical management. To achieve this, a cross-sectional study was conducted to investigate factors influencing nutrition status using GLIM criteria and explore the 180-day readmission factors among hospitalized elderly COPD patients. METHORDS AND RESULTS: The data were collected from a hospital in Southwest China, encompassing a cohort of 319 eligible patients. Among elderly hospitalized COPD patients, the prevalence of malnutrition was 49.53% (158/319). Multivariate logistic regression revealed malnutrition (OR = 3.184), very severe airway obstruction (OR = 3.735), and Number of comorbidities ≥ 3 (OR = 5.754) as significant risk factors for 180-day readmission. CONCLUSIONS: These findings suggest that malnutrition is a prevalent issue among elderly hospitalized patients with COPD and constitutes one of the risk factors contributing to the 180-day readmission rate. Therefore, timely identification and treatment for malnourished patients are crucial.


Asunto(s)
Desnutrición , Estado Nutricional , Readmisión del Paciente , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Anciano , Masculino , Femenino , Readmisión del Paciente/estadística & datos numéricos , Desnutrición/epidemiología , Estudios Transversales , Factores de Riesgo , Anciano de 80 o más Años , Hospitalización/estadística & datos numéricos , Prevalencia , China/epidemiología , Comorbilidad
2.
J Environ Manage ; 325(Pt A): 116500, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36265231

RESUMEN

The spatial planning and sustainable management of peri-urban cultivated land are key aspects of national development in many countries because of the continuing expansion of urban areas and deterioration of agro-ecosystem services. Detailed geo-informational investigation of cultivated land multifunctionality and the spatial interactions and dependencies of these multiple functions is required to inform the currently weak theoretical framework of multifunctionality at the peri-urban scale. Accordingly, the objective of this study was to construct a comprehensive methodology to identify and evaluate cultivated land multifunctionality in a spatial context. Geochemical data were used to measure cultivated land multifunctionality. We evaluated two main functions-the productive function and the ecological function-of an undeveloped peri-urban agriculture (PUA) area in the northern fringe of Changchun City in the black-soil region of northeastern China. For the ecological utilization of PUA areas, tradeoff and synergy analyses of cultivated land multifunctionality and coordinated development under complex land-use patterns were measured using a bivariate local Moran's I method. Results reveal considerable spatial heterogeneity in the two functions, with hotspots or coldspots being found in the PUA area. The productive function presents a less pronounced decreasing trend along the rural-to-urban gradient compared with the ecological function. Tradeoffs and synergies between the productive function and the ecological function occur mainly in the northern (more rural) part of the PUA area, where the spatial spillover effect of urbanization is relatively low. Cultivated land functions are strongly affected by urbanization-induced land-use types, and the coordinated areas of the productive function are generally consistent with those of the ecological function. According to these results, we delineate nine zones of multifunctionality in the studied PUA area. Given the importance of harmonizing cultivated land multifunctionality to manage limited land resources in a sustainable way, application of the GIS- and geochemistry-based multifunctionality evaluation scheme proposed in this study should be used to guide peri-urban spatial planning and land-use management and inform the policy arena concerning the transition of land use in urban peripheries.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Agricultura , Urbanización , China , Ciudades
3.
Int J Mol Sci ; 23(23)2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36499574

RESUMEN

Carboxycellulose nanofibers (CNFs) promise to be a sustainable and inexpensive alternative material for polymer electrolyte membranes compared to the expensive commercial Nafion membrane. However, its practical applications have been limited by its relatively low performance and reduced mechanical properties under typical operating conditions. In this study, carboxycellulose nanofibers were derived from wood pulp by TEMPO oxidation of the hydroxyl group present on the C6 position of the cellulose chain. Then, citric acid cross-linked CNF membranes were prepared by a solvent casting method to enhance performance. Results from FT-IR spectroscopy, 13C NMR spectroscopy, and XRD reveal a chemical cross-link between the citric acid and CNF, and the optimal fuel cell performance was obtained by cross-linking 70 mL of 0.20 wt % CNF suspension with 300 µL of 1.0 M citric acid solution. The membrane electrode assemblies (MEAs), operated in an oxygen atmosphere, exhibited the maximum power density of 27.7 mW cm-2 and the maximum current density of 111.8 mA cm-2 at 80 °C and 100% relative humidity (RH) for the citric acid cross-linked CNF membrane with 0.1 mg cm-2 Pt loading on the anode and cathode, which is approximately 30 times and 22 times better, respectively, than the uncross-linked CNF film. A minimum activation energy of 0.27 eV is achieved with the best-performing citric acid cross-linked CNF membrane, and a proton conductivity of 9.4 mS cm-1 is obtained at 80 °C. The surface morphology of carboxycellulose nanofibers and corresponding membranes were characterized by FIB/SEM, SEM/EDX, TEM, and AFM techniques. The effect of citric acid on the mechanical properties of the membrane was assessed by tensile strength DMA.


Asunto(s)
Nanofibras , Espectroscopía Infrarroja por Transformada de Fourier , Nanofibras/química , Celulosa/química , Resistencia a la Tracción , Ácido Cítrico
4.
PLoS One ; 19(9): e0306097, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39231169

RESUMEN

Reducing the environmental pressures stemming from food production is central to meeting global sustainability targets. Shifting diets represents one lever for improving food system sustainability, and identifying sustainable diet opportunities requires computational models to represent complex systems and allow users to evaluate counterfactual scenarios. Despite an increase in the number of food system sustainability models, there remains a lack of transparency of data inputs and mathematical formulas to facilitate replication by researchers and application by diverse stakeholders. Further, many models lack the ability to model multiple geographic scales. The present study introduces Foodprint 2.0, which fills both gaps. Foodprint 2.0 is an updated biophysical simulation model that estimates the agricultural resource requirements of diet patterns and can be adapted to suit a variety of research purposes. The objectives of this study are to: 1) describe the new features of Foodprint 2.0, and 2) demonstrate model performance by estimating the agricultural resource requirements of food demand in the United States (US) using nationally representative dietary data from the National Health and Nutrition Examination Survey from 2009-2018. New features of the model include embedded functions to integrate individual-level dietary data that allow for variance estimation; new data and calculations to account for the resource requirements of food trade and farmed aquatic food; updated user interface; expanded output data for over 200 foods that include the use of fertilizer nutrients, pesticides, and irrigation water; supplementary files that include input data for all parameters on an annual basis from 1999-2018; sample programming code; and step-by-step instructions for users. This study demonstrates that animal-sourced foods consumed in the US accounted for the greatest share of total land use, fertilizer nutrient use, pesticide use, and irrigation water use, followed by grains, fruits, and vegetables. Greater adherence to the Dietary Guidelines for Americans was associated with lower use of land and fertilizer nutrients, and greater use of pesticides and irrigation water. Foodprint 2.0 is a highly modifiable model that can be a useful resource for informing sustainable diet policy discussions.


Asunto(s)
Agricultura , Simulación por Computador , Dieta , Humanos , Agricultura/métodos , Abastecimiento de Alimentos , Estados Unidos , Encuestas Nutricionales , Modelos Teóricos
5.
Dev Cell ; 59(8): 1010-1027.e8, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38569549

RESUMEN

Ten-eleven translocation (TET) enzymes iteratively oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during mammalian germline reprogramming remains unresolved due to the inability to decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V). Tet1 knockout and catalytic mutant primordial germ cells (PGCs) fail to erase methylation at select imprinting control regions and promoters of meiosis-associated genes, validating the requirement for the iterative oxidation of 5mC for complete germline reprogramming. TET1V and TET1HxD rescue most hypermethylation of Tet1-/- sperm, suggesting the role of TET1 beyond its oxidative capability. We additionally identify a broader class of hypermethylated regions in Tet1 mutant mouse sperm that depend on TET oxidation for reprogramming. Our study demonstrates the link between TET1-mediated germline reprogramming and sperm methylome patterning.


Asunto(s)
5-Metilcitosina , 5-Metilcitosina/análogos & derivados , Metilación de ADN , Proteínas de Unión al ADN , Impresión Genómica , Oxidación-Reducción , Proteínas Proto-Oncogénicas , Espermatozoides , Animales , Masculino , Ratones , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Espermatozoides/metabolismo , 5-Metilcitosina/metabolismo , Reprogramación Celular/genética , Ratones Noqueados , Ratones Endogámicos C57BL
6.
Int Immunopharmacol ; 142(Pt A): 113027, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39216119

RESUMEN

OBJECTIVE: This study aimed to elucidate the causal relationships between antibodies and autoimmune diseases using Mendelian randomization (MR). METHODS: Data on 46 antibodies were obtained from genome-wide association studies (GWAS). Autoimmune disease data were sourced from the FinnGen consortium and the IEU OpenGWAS project. Inverse-variance weighted (IVW) analysis was the primary method, supplemented by heterogeneity and sensitivity analyses. We also examined gene expression near significant SNPs and conducted drug sensitivity analyses. RESULTS: Antibodies and autoimmune diseases exhibit diverse interactions. Antibodies produced after Polyomavirus infection tend to increase the risk of several autoimmune diseases, while those following Human herpesvirus 6 infection generally reduce it. The impact of Helicobacter pylori infection varies, with different antibodies affecting autoimmune diseases in distinct ways. Overall, antibodies significantly influence the risk of developing autoimmune diseases, whereas autoimmune diseases have a lesser impact on antibody levels. Gene expression and drug sensitivity analyses identified multiple genes and drugs as potential treatment options for ankylosing spondylitis (AS), with the AIF1 gene being particularly promising. CONCLUSIONS: Bidirectional MR analysis confirms complex causal relationships between various antibodies and autoimmune diseases, revealing intricate patterns of post-infection antibody interactions. Several drugs and genes, notably AIF1, show potential as candidates for AS treatment, offering new avenues for research. Further exploration of the underlying mechanisms is necessary.


Asunto(s)
Enfermedades Autoinmunes , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/genética , Perfilación de la Expresión Génica , Polimorfismo de Nucleótido Simple , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/inmunología
7.
bioRxiv ; 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36865267

RESUMEN

DNA methylation erasure is required for mammalian primordial germ cell reprogramming. TET enzymes iteratively oxidize 5-methylcytosine to generate 5-hyroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxycytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during germline reprogramming remains unresolved due to the lack of genetic models that decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 ( Tet1-HxD ) and TET1 that stalls oxidation at 5hmC ( Tet1-V ). Tet1 -/- , Tet1 V/V , and Tet1 HxD/HxD sperm methylomes show that TET1 V and TET1 HxD rescue most Tet1 -/- hypermethylated regions, demonstrating the importance of TET1’s extra-catalytic functions. Imprinted regions, in contrast, require iterative oxidation. We further reveal a broader class of hypermethylated regions in sperm of Tet1 mutant mice that are excluded from de novo methylation during male germline development and depend on TET oxidation for reprogramming. Our study underscores the link between TET1-mediated demethylation during reprogramming and sperm methylome patterning.

8.
Front Microbiol ; 13: 957698, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35910649

RESUMEN

Antimicrobial photodynamic inactivation (aPDI) is a newly emerged treatment approach that can effectively address the issue of multidrug resistance resulting from the overuse of antibiotics. Fullerenes can be used as promising photosensitizers (PSs) for aPDI due to the advantages of high triplet state yields, good photostability, wide antibacterial spectrum, and permissibility of versatile functionalization. This review introduces the photodynamic activities of fullerenes and the up-to-date understanding of the antibacterial mechanisms of fullerene-based aPDI. The most recent works on the functionalization of fullerenes and the application of fullerene derivatives as PSs for aPDI are also summarized. Finally, certain remaining challenges are emphasized to provide guidance on future research directions for achieving clinical application of fullerene-based aPDI.

9.
Huan Jing Ke Xue ; 43(1): 454-462, 2022 Jan 08.
Artículo en Zh | MEDLINE | ID: mdl-34989530

RESUMEN

Agricultural products are a primary pathway for humans to accumulate heavy metals (HMs) via the soil-crop system and should therefore should be included as a crucial part of the food security in our country. Given that previous studies on protection zoning for preventing farmland HM pollution rarely considered agricultural products as a basic element, this study attempted to establish a zoning system for farmland HM prevention, which was based on the perspective of agricultural product pollution. We subsequently took a representative peri-urban area in the black soil region, which was provided with a higher risk of being polluted, as an empirical case. The results indicated that:① the comprehensive quality index of agricultural products (IICQAP) was 1.09, illustrating only a mild HM pollution, with Pb and Ni having the highest accumulation levels; ② the human health risk index (QHI) was 0.61, showing no risk for human health; and ③ the designed zoning method revealed 89.45% of the farmlands to be risk-free at the moment and 10.55% of the farmlands to be under low risk of HM pollution in agricultural products. According to the zoning results, we suggested prioritized protection and an early-warning strategy, respectively, and further recommended prevention methods such as accumulation intervention, crop restructuring, and in-situ passivation. The results served to enrich the theoretical basis for preventing farmland HM pollution, to reinforce the management standards for agricultural products in the black soil region, and also to build a differentiated urban-rural farmland protection system.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , China , Monitoreo del Ambiente , Granjas , Humanos , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis
10.
Biointerphases ; 16(1): 011003, 2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33706527

RESUMEN

Biofouling on material surfaces is a ubiquitous problem in a variety of fields. In aqueous environments, the process of biofouling initiates with the formation of a layer of macromolecules called the conditioning layer on the solid-liquid interface, followed by the adhesion and colonization of planktonic bacteria and the subsequent biofilm development and maturation. In this study, the extracellular polymeric substances (EPS) secreted by Bacillus subtilis were collected and used to prepare conditioning layers on inert surfaces. The morphologies and antifouling performances of the EPS conditioning layers were investigated. It was found that the initial adhesion of Escherichia coli was inhibited on the surfaces precoated with EPS conditioning layers. To further explore the underlying antifouling mechanisms of the EPS conditioning layers, the respective roles of two constituents of B. subtilis EPS (γ-polyglutamic acid and surfactin) were investigated. This study has provided the possibility of developing a novel interfacial antifouling additive with the advantages of easy preparation, nontoxicity, and environmental friendliness.


Asunto(s)
Bacillus subtilis/química , Adhesión Bacteriana , Incrustaciones Biológicas , Escherichia coli/citología , Matriz Extracelular de Sustancias Poliméricas/química , Silicio/farmacología , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Escherichia coli/ultraestructura , Ácido Poliglutámico/farmacología , Propiedades de Superficie
11.
Front Bioeng Biotechnol ; 9: 650598, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33681176

RESUMEN

Skin wounds not only cause physical pain for patients but also are an economic burden for society. It is necessary to seek out an efficient approach to promote skin repair. Hydrogels are considered effective wound dressings. They possess many unique properties like biocompatibility, biodegradability, high water uptake and retention etc., so that they are promising candidate materials for wound healing. Chitosan is a polymeric biomaterial obtained by the deacetylation of chitin. With the properties of easy acquisition, antibacterial and hemostatic activity, and the ability to promote skin regeneration, hydrogel-like functional wound dressings (represented by chitosan and its derivatives) have received extensive attentions for their effectiveness and mechanisms in promoting skin wound repair. In this review, we extensively discussed the mechanisms with which chitosan-based functional materials promote hemostasis, anti-inflammation, proliferation of granulation in wound repair. We also provided the latest information about the applications of such materials in wound treatment. In addition, we summarized the methods to enhance the advantages and maintain the intrinsic nature of chitosan via incorporating other chemical components, active biomolecules and other substances into the hydrogels.

12.
ACS Appl Bio Mater ; 2(12): 5957-5964, 2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-35021516

RESUMEN

Bacterial infection has been one of the main obstacles for extensive biomedical applications of biomaterial films. Understanding the interactions among macromolecules, cells, and bacteria in the microenvironment located on the film surface at the molecular level is essential for developing antibacterial films. Here we report the distinct influence of several key serum proteins adsorbed on diamond-like carbon (DLC) and traditional Ti films on initial bacterial adhesion, biofilm formation, and corresponding immune responses. Type I collagen, Fn, and IgG were selected as the typical serum proteins. Gram-positive bacterium Staphylococcus epidermidis and Gram-negative bacterium Escherichia coli were used as the model bacteria. Macrophage phagocytosis tests were carried out to examine the impact of adsorbed proteins on the ability of macrophages to clear the adhered pathogens. Results show that it was the specific molecular recognition between adsorbed proteins and bacteria, not the surface physiochemical properties such as surface wettability, surface roughness, and surfaces charge, that decisively affected bacterial adhesion and following biofilm formation. Collagen resisted bacterial adhesion on both DLC and Ti films, even though the molecules exhibited distinct conformations on the two surfaces, whereas for Fn and IgG, the specific molecular recognition was closely related to protein conformations. Fn molecules formed globular aggregates on Ti surfaces that greatly enhanced bacterial adhesion but exhibited a fibril conformation on DLC surfaces that inhibited bacterial adhesion. IgG showed an end-on orientation with free F(ab)2 domains on Ti surfaces, facilitating bacterial adhesion and biofilm formation, while the flattened orientation on DLC films showed little effect on bacterial behaviors. Furthermore, preadsorption of Fn and IgG significantly promoted the phagocytosis ability of macrophages against S. epidermidis and affected the corresponding secretion of inflammatory cytokine. These results would give insights into understanding protein-surface interactions for developing appropriate surface modification techniques for biomaterials with desired anti-inflammatory functions.

13.
Chem Asian J ; 14(13): 2220-2224, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31081238

RESUMEN

Water-soluble ratiometric AIE-active fluorescent organic nanoparticles 2OA-FON for the specific sensing of cysteine over other biothiols are reported. The obtained amphiphilic probe included olefin aldehyde as recognizing unit, tetraphenylethylene as fluorescence reporter and lactose moiety as a hydrophilic group. This work provides a general design strategy based on the introduction of a sugar moiety into a hydrophobic AIEgen to develop ratiometric water-soluble fluorescent organic nanoparticles.


Asunto(s)
Cisteína/análisis , Colorantes Fluorescentes/química , Glutatión/análisis , Homocisteína/análisis , Nanopartículas/química , Estilbenos/química , Dimerización , Células Hep G2 , Humanos , Microscopía Confocal , Nanopartículas/ultraestructura , Imagen Óptica , Solubilidad , Espectrometría de Fluorescencia , Agua/química
14.
Biointerphases ; 13(6): 060801, 2018 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-30482024

RESUMEN

Bacterial adhesion and biofilm formation are ubiquitous undesirable phenomena in the marine industry and the medical industry, usually causing economic losses and serious health problems. Numerous efforts have been made to reduce bacterial adhesion and subsequent biofilm formation, most of which are based on the release of toxic biocides from coatings or substrates. In recent years, surface topography has been found to substantially influence the interaction between bacteria and surfaces. This review summarizes previous work dedicated in searching for the relationship between bacterial adhesion and surface topography in the last eight years, as well as the proposed mechanisms by which surface topographic features interact with bacterial cells. Next, various natural and artificial surfaces with bactericidal surface topography along with their bactericidal mechanisms and efficiency are introduced. Finally, the technologies for constructing antibacterial surfaces are briefly summarized.


Asunto(s)
Adhesión Bacteriana , Biopelículas/crecimiento & desarrollo , Propiedades de Superficie , Fenómenos Químicos , Microbiología Ambiental , Viabilidad Microbiana
15.
Zhonghua Nei Ke Za Zhi ; 44(1): 9-12, 2005 Jan.
Artículo en Zh | MEDLINE | ID: mdl-15769388

RESUMEN

OBJECTIVE: To study the clinical characteristics of fulminate pancreatitis (FP) and analysis the factors related to prognosis of FP. METHODS: Data of 203 patients with severe acute pancreatitis (SAP) admitted to our hospital within 72 h after onset of symptoms from January 2000 to December 2002 were reviewed. FP was defined as presence of organ dysfunction within 72 h after onset of symptoms. 78 patients had FP, 125 patients without organ dysfunction within 72 h after onset of symptoms had common severe acute pancreatitis (CSAP). The clinical characteristics, incidence of organ dysfunction during hospitalization and prognosis between FP and CSAP were compared, then the factors related to prognosis of FP were analysed. RESULTS: The incidences of T >/= 38.5 degrees C, hypoxemia, shock, white cell count >/= 16 x 10(9)/L, serum calcium < 2.0 mmol/L and multiple organ dysfunction syndrome (MODS) in FP were higher than those in CSAP (71.8% vs 39.2%, 83.3% vs 30.4%, 41.0% vs 12.0%, 64.1% vs 30.4%, 68.0% vs 44.8%, 73.1% vs 11.2%, P < 0.05). Impairment degree of pancreas (Balthazar CT severity index) in FP was more serious than that in CSAP (5.78 +/- 0.83 vs 3.12 +/- 0.57, P < 0.05). FP had a higher mortality than CSAP (44.9% vs 8.8%, P < 0.05). In multiple logistic regression analysis, the main predisposing factors to FP were hypoxemia, MODS and Balthazar CT severity index. CONCLUSIONS: FP is characterised by severe systemic inflammatory response, severe pathological changes of pancreas, high incidence of MODS and high mortality. The main predisposing factors to FP were hypoxemia, MODS and Balthazar CT severity index.


Asunto(s)
Pancreatitis/diagnóstico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Hipoxia/diagnóstico , Hipoxia/mortalidad , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/mortalidad , Pancreatitis/mortalidad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
16.
Mol Med Rep ; 11(6): 4121-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25672589

RESUMEN

The persistent administration of ß2­adrenergic (ß2AR) agonists has been demonstrated to increase the risk of severe asthma, partly due to the induction of tolerance to bronchoprotection via undefined mechanisms. The present study investigated the potential effect of the long­acting ß2­adrenergic agonist, formoterol, on the expression of muscarinic M3 receptor (M3R) in rat airway smooth muscle cells (ASMCs). Primary rat ASMCs were isolated and characterized following immunostaining with anti­α­smooth muscle actin antibodies. The protein expression levels of M3R and phospholipase C­ß1 (PLCß1) were characterized by western blot analysis and the production of inositol 1,4,5­trisphosphate (IP3) was determined using an enzyme­linked immunosorbent assay. Formoterol increased the protein expression of M3R in rat ASMCs in a time­ and dose­dependent manner, which was significantly inhibited by the ß2AR antagonist, ICI118,551 and the cyclic adenosine monophosphate (cAMP) inhibitor, SQ22,536. The increased protein expression of M3R was positively correlated with increased production of PLCß1 and IP3. Furthermore, treatment with the glucocorticoid, budesonide, and the PLC inhibitor, U73,122, significantly suppressed the formoterol­induced upregulated protein expression levels of M3R and PLCß1 and production of IP3. The present study demonstrated that formoterol mediated the upregulation of M3R in the rat ASMCs by activating the ß2AR­cAMP signaling pathway, resulting in increased expression levels of PLCß1 and IP3, which are key to inducing bronchoprotection tolerance. Administration of glucocorticoids or a PLC antagonist prevented formoterol­induced bronchoprotection tolerance by suppressing the protein expression of M3R.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/farmacología , AMP Cíclico/metabolismo , Fumarato de Formoterol/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Receptor Muscarínico M3/metabolismo , Animales , Células Cultivadas , Masculino , Miocitos del Músculo Liso/metabolismo , Ratas Wistar , Transducción de Señal/efectos de los fármacos
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