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1.
J Mol Recognit ; 37(4): e3085, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599335

RESUMO

Many proteins could aggregate into amyloid fibrils under certain conditions. However, the aggregation process and morphology of the fibrils may be significantly different because of the distinct protein structure. In this article, the hydrophilic carbon dots (Lys-CA-CDs) were prepared using lysine (Lys) and citric acid (CA) as reactant under the assistance of a microwave. The dissimilar modulation effect of Lys-CA-CDs on the aggregation process of distinct structure protein was further investigated, where bovine serum albumin (BSA) and hen egg white lysozyme (HEWL) were chosen as model proteins. All results showed that Lys-CA-CDs displayed the contrary influence on the aggregation process of BSA and HEWL. Lys-CA-CDs could induce BSA to aggregate into more wormlike fibrils and inhibit the aggregation of HEWL into hair-like fibrils. The influence on the aggregation process of BSA may be assigned to the increased concentration of BSA around the Lys-CA-CDs caused by their interaction. However, inserting of Lys-CA-CDs into the inner structure of HEWL led to the change of protein secondary structure. The change of secondary structure further made it difficult for HEWL to aggregate into fibrils and Lys-CA-CDs showed the inhibition effect on HEWL aggregation.


Assuntos
Amiloide , Carbono , Interações Hidrofóbicas e Hidrofílicas , Muramidase , Agregados Proteicos , Soroalbumina Bovina , Muramidase/química , Muramidase/metabolismo , Carbono/química , Soroalbumina Bovina/química , Amiloide/química , Animais , Agregados Proteicos/efeitos dos fármacos , Bovinos , Lisina/química , Estrutura Secundária de Proteína , Pontos Quânticos/química , Galinhas , Ácido Cítrico/química
2.
Opt Express ; 32(11): 18771-18789, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859027

RESUMO

Reconstructing high-quality images at a low measurement rate is a pivotal objective of Single-Pixel Imaging (SPI). Currently, deep learning methods achieve this by optimizing the loss between the target image and the original image, thereby constraining the potential of low measurement values. We employ conditional probability to ameliorate this, introducing the classifier-free guidance model (CFG) for enhanced reconstruction. We propose a self-supervised conditional masked classifier-free guidance (SCM-CFG) for single-pixel reconstruction. At a 10% measurement rate, SCM-CFG efficiently completed the training task, achieving an average peak signal-to-noise ratio (PSNR) of 26.17 dB on the MNIST dataset. This surpasses other methods of photon imaging and computational ghost imaging. It demonstrates remarkable generalization performance. Moreover, thanks to the outstanding design of the conditional mask in this paper, it can significantly enhance the accuracy of reconstructed images through overlay. SCM-CFG achieved a notable improvement of an average of 7.3 dB in overlay processing, in contrast to only a 1 dB improvement in computational ghost imaging. Subsequent physical experiments validated the effectiveness of SCM-CFG.

3.
Cell Commun Signal ; 22(1): 50, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233928

RESUMO

AIMS: Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process. METHODS: As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients' blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs. RESULTS: A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients' neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model. CONCLUSIONS: NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS. Video Abstract.


Assuntos
Lesões Encefálicas , Armadilhas Extracelulares , Proteína HMGB1 , AVC Isquêmico , Trombose , Animais , Camundongos , Humanos , Armadilhas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Trombose/metabolismo , Neutrófilos , Lesões Encefálicas/metabolismo
4.
J Microsc ; 293(3): 169-176, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38112123

RESUMO

Gallium ion (Ga+ ) beam damage induced indium (In) precipitation in indium gallium arsenide (InGaAs)/indium aluminium arsenide (InAlAs) multiple quantum wells and its corresponding evolution under electron beam irradiation was investigated by valence electron energy loss spectroscopy (VEELS) and high-angle annular dark-field imaging (HAADF) in scanning transmission electron microscopy (STEM). Compared with argon ion milling for sample preparation, the heavier projectiles of Ga+ ions pose a risk to trigger In formation in the form of tiny metallic In clusters. These are shown to be sensitive to electron irradiation and can increase in number and size under the electron beam, deteriorating the structure. Our finding reveals the potential risk of formation of In clusters during focused ion beam (FIB) preparation of InGaAs/InAlAs quantum well samples and their subsequent growth under STEM-HAADF imaging, where initially invisible In clusters of a few atoms can move and swell during electron beam exposure.

5.
Biochem Genet ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536568

RESUMO

Cancer-associated fibroblasts (CAFs) are an important component of the stroma. Studies showed that CAFs were pivotally in glioma progression which have long been considered a promising therapeutic target. Therefore, the identification of prognostic CAF markers might facilitate the development of novel diagnostic and therapeutic approaches. A total of 1333 glioma samples were obtained from the TCGA and CGGA datasets. The EPIC, MCP-counter, and xCell algorithms were used to evaluate the relative proportion of CAFs in glioma. CAF markers were identified by the single-cell RNA-seq datasets (GSE141383) from the Tumor Immune Single-Cell Hub database. Unsupervised consensus clustering was used to divide the glioma patients into different distinct subgroups. The least absolute shrinkage and selection operator regression model was utilized to establish a CAF-related signature (CRS). Finally, the prognostic CAF markers were further validated in clinical specimens by RT‒qPCR. Combined single-cell RNA-seq analysis and differential expression analysis of samples with high and low proportions of CAFs revealed 23 prognostic CAF markers. By using unsupervised consensus clustering, glioma patients were divided into two distinct subtypes. Subsequently, based on 18 differentially expressed prognostic CAF markers between the two CAF subtypes, we developed and validated a new CRS model (including PCOLCE, TIMP1, and CLIC1). The nomogram and calibration curves indicated that the CRS was an accurate prognostic marker for glioma. In addition, patients in the high-CRS score group had higher immune infiltration and tumor mutation burden levels. Moreover, the CRS score had the potential to predict the response to immune checkpoint blockade (ICB) therapy and chemotherapy. Finally, the expression profiles of three CAF markers were verified by RT‒qPCR. In general, our study classified glioma patients into distinct subgroups based on CAF markers, which will facilitate the development of individualized therapy. We also provided insights into the role of the CRS in predicting the response to ICB and chemotherapy in glioma patients.

6.
Sensors (Basel) ; 24(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38400260

RESUMO

X-ray computed tomography (XCT) has become a powerful technique for studying lithium-ion batteries, allowing non-destructive 3D imaging across multiple spatial scales. Image quality is particularly important for observing the internal structure of lithium-ion batteries. During multiple rotations, the existence of cumulative errors and random errors in the rotary table leads to errors in the projection angle, affecting the imaging quality of XCT. The accuracy of the projection angle is an important factor that directly affects imaging. However, the impact of the projection angle on XCT reconstruction imaging is difficult to quantify. Therefore, the required precision of the projection angle sensor cannot be determined explicitly. In this research, we selected a common 18650 cylindrical lithium-ion battery for experiments. By setting up an XCT scanning platform and installing an angle sensor to calibrate the projection angle, we proceeded with image reconstruction after introducing various angle errors. When comparing the results, we found that projection angle errors lead to the appearance of noise and many stripe artifacts in the image. This is particularly noticeable in the form of many irregular artifacts in the image background. The overall variation and residual projection error in detection indicators can effectively reflect the trend in image quality. This research analyzed the impact of projection angle errors on imaging and improved the quality of XCT imaging by installing angle sensors on a rotary table.

7.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38279235

RESUMO

The presence of the ozone hole increases the amount of UV radiation reaching a plant's surface, and UV-B radiation is an abiotic stress capable of affecting plant growth. Rhododendron chrysanthum Pall. (R. chrysanthum) grows in alpine regions, where strong UV-B radiation is present, and has been able to adapt to strong UV-B radiation over a long period of evolution. We investigated the response of R. chrysanthum leaves to UV-B radiation using widely targeted metabolomics and transcriptomics. Although phytohormones have been studied for many years in plant growth and development and adaptation to environmental stresses, this paper is innovative in terms of the species studied and the methods used. Using unique species and the latest research methods, this paper was able to add information to this topic for the species R. chrysanthum. We treated R. chrysanthum grown in a simulated alpine environment, with group M receiving no UV-B radiation and groups N and Q (externally applied abscisic acid treatment) receiving UV-B radiation for 2 days (8 h per day). The results of the MN group showed significant changes in phenolic acid accumulation and differential expression of genes related to phenolic acid synthesis in leaves of R. chrysanthum after UV-B radiation. We combined transcriptomics and metabolomics data to map the metabolic regulatory network of phenolic acids under UV-B stress in order to investigate the response of such secondary metabolites to stress. L-phenylalanine, L-tyrosine and phenylpyruvic acid contents in R. chrysanthum were significantly increased after UV-B radiation. Simultaneously, the levels of 3-hydroxyphenylacetic acid, 2-phenylethanol, anthranilate, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, α-hydroxycinnamic acid and 2-hydroxy-3-phenylpropanoic acid in this pathway were elevated in response to UV-B stress. In contrast, the study in the NQ group found that externally applied abscisic acid (ABA) in R. chrysanthum had greater tolerance to UV-B radiation, and phenolic acid accumulation under the influence of ABA also showed greater differences. The contents of 2-phenylethanol, 1-o-p-coumaroyl-ß-d-glucose, 2-hydroxy-3-phenylpropanoic acid, 3-(4-hydroxyphenyl)-propionic acid and 3-o-feruloylquinic ac-id-o-glucoside were significantly elevated in R. chrysanthum after external application of ABA to protect against UV-B stress. Taken together, these studies of the three groups indicated that ABA can influence phenolic acid production to promote the response of R. chrysanthum to UV-B stress, which provided a theoretical reference for the study of its complex molecular regulatory mechanism.


Assuntos
Glucose , Hidroxibenzoatos , Álcool Feniletílico , Fenilpropionatos , Rhododendron , Ácido Abscísico/metabolismo , Rhododendron/genética , Ácidos Cumáricos , Raios Ultravioleta
8.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33594424

RESUMO

m6A RNA methylation is an emerging epigenetic modification, and its potential role in immunity and stemness remains unknown. Based on 17 widely recognized m6A regulators, the m6A modification patterns and corresponding characteristics of immune infiltration and stemness of 1152 low-grade glioma samples were comprehensively analyzed. Machine-learning strategies for constructing m6AScores were trained to quantify the m6A modification patterns of individual samples. Here, we reveal a significant correlation between the multi-omics data of regulators and clinicopathological parameters. We identified two distinct m6A modification patterns (an immune-activated differentiation pattern and an immune-desert dedifferentiation pattern) and four regulatory patterns of m6A methylation on immunity and stemness. We show that the m6AScores can predict the molecular subtype of low-grade glioma, the abundance of immune infiltration, the enrichment of signaling pathways, gene variation and prognosis. The concentration of high immunogenicity and clinical benefits in the low-m6AScore group confirmed the sensitive response to radio-chemotherapy and immunotherapy in patients with high-m6AScore. The results of the pan-cancer analyses illustrate the significant correlation between m6AScore and clinical outcome, the burden of neoepitope, immune infiltration and stemness. The assessment of individual tumor m6A modification patterns will guide us in improving treatment strategies and developing objective diagnostic tools.


Assuntos
Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Glioma/genética , Glioma/imunologia , Imunidade Inata , Metiltransferases/genética , Proteínas de Ligação a RNA/genética , Adenosina/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Variações do Número de Cópias de DNA , Epigênese Genética , Glioma/patologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Aprendizado de Máquina , Taxa de Mutação , Fenótipo , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
9.
Environ Sci Technol ; 56(23): 17153-17165, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36242560

RESUMO

Dermal penetration potentials of titanium dioxide nanoparticles (TiO2 NPs) may be affected by aggregation upon contact with sweat. This study investigated the aggregation kinetics of three TiO2 NPs in thirty human sweat samples and four artificial sweat standards. Effects of particle concentration, sweat type, and inorganic (sodium chloride, disodium hydrogen phosphate, and sodium dihydrogen phosphate) and organic (l-histidine, lactic acid, and urea) constituents were examined. Three TiO2 NPs remained colloidally stable in >20/30 human sweat samples and showed significant negative correlations (P < 0.01) between aggregation rates and |zeta potentials|. They aggregated rapidly over 20 min to >750 nm in three artificial sweat standards, while remained more stable in the International-Standard-Organization-pH-5.5 standard. Aggregation behaviors of three TiO2 NPs mostly followed the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, allowing for determining their critical coagulation concentrations in inorganic constituents (15-491 mM) and Hamaker constants (3.3-7.9 × 10-21 J). Higher concentrations of particles, inorganic constituents, and l-histidine destabilized three TiO2 NPs, whereas urea inhibited aggregation. Three TiO2 NPs adsorbed organic sweat constituents via complexation with amino or carboxyl groups, with isotherms following the Langmuir model. Correlation analyses further suggested that the adsorbed organic constituents may stabilize three TiO2 NPs against aggregation in sweat by steric hindrance.


Assuntos
Nanopartículas , Suor , Humanos , Histidina , Titânio , Cinética , Ureia
10.
Mol Biol Rep ; 49(1): 303-312, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34743272

RESUMO

BACKGROUND: As an alpine plant, Rhododendron chrysanthum (R. chrysanthum) has evolved cold resistance mechanisms and become a valuable plant resource with the responsive mechanism of cold stress. METHODS AND RESULTS: We adopt the phosphoproteomic and proteomic analysis combining with physiological measurement to illustrate the responsive mechanism of R. chrysanthum seedling under cold (4 °C) stress. After chilling for 12 h, 350 significantly changed proteins and 274 significantly changed phosphoproteins were detected. Clusters of Orthologous Groups (COG) analysis showed that significantly changed phosphoproteins and proteins indicated cold changed energy production and conversion and signal transduction. CONCLUSIONS: The results indicated photosynthesis was inhibited under cold stress, but cold induced calcium-mediated signaling, reactive oxygen species (ROS) homeostasis and other transcription regulation factors could protect plants from the destruction caused by cold stress. These data provide the insight to the cold stress response and defense mechanisms of R. chrysanthum leaves at the phosphoproteome level.


Assuntos
Fosfoproteínas/química , Fosfoproteínas/metabolismo , Proteômica/métodos , Rhododendron/crescimento & desenvolvimento , Sinalização do Cálcio , Resposta ao Choque Frio , Regulação da Expressão Gênica , Modelos Moleculares , Fotossíntese , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Conformação Proteica , Espécies Reativas de Oxigênio/metabolismo , Rhododendron/metabolismo
11.
Chemistry ; 25(67): 15411-15418, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31489999

RESUMO

A divergent strategy for the facile preparation of various enantioenriched phenylthio-substituted lactones was developed based on Lewis base/Brønsted acid co-catalyzed thiolation of homoallylic acids. The acid-controlled regiodivergent cyclization (6-endo vs. 5-exo) and acid-mediated stereoselective rearrangement of phenylthio-substituted lactones were explored. Experimental and computational studies were performed to clarify the origins of the regioselectivity and enantioselectivity. The calculation results suggest that C-O and C-S bond formation might occur simultaneously, without formation of a commonly supposed catalyst-coordinated thiiranium ion intermediate and the potential π-π stacking between substrate and SPh as an important factor in the enantio-determining step. Finally, this methodology was applied in the rapid syntheses of the bioactive natural products (+)-ricciocarpin A and (R)-dodecan-4-olide.

12.
Angew Chem Int Ed Engl ; 57(40): 13192-13196, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30126040

RESUMO

An efficient oximation method has been developed on the basis of NO+ -initiated semipinacol rearrangement and subsequent proton elimination. The procedure enabled the rapid construction of a series of oximes and oxime ethers with spiro quaternary stereocenters from allylic silyl ethers. Additional features of this reaction include wide substrate tolerance as well as the commercial availability of the safe nitrosation reagent NOBF4 . The key N-heterotricyclic cores of three natural alkaloids, tuberostemoninol B, (+)-quebrachidine, and an insecticide, were also constructed efficiently by this method.

13.
J Org Chem ; 80(5): 2925-9, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25664805

RESUMO

An efficient synthesis of phenols via Pd-catalyzed, pyridyl-directed homogeneous hydroxylation of the aryl C-H bond was developed, in which tert-butyl hydroperoxide was used as the sole oxidant. The method had a broad group tolerance and was available for both electron-rich and electron-deficient substrates. The reaction of a series of 2-arylpyridine derivatives gave the ortho-hydroxylation products in moderate to good yields.

14.
J Org Chem ; 80(24): 12588-93, 2015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26539743

RESUMO

2-(Alkylamino)benzonitriles were synthesized via a rhodium-catalyzed cyanation on the aryl C-H bond and subsequent denitrosation of N-nitrosoarylamines using a removable nitroso as the directing group, in which N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) was used as the "CN" source. Various substituents on the aryl ring and amino group of N-nitrosoarylamines tolerated the reaction, and the corresponding products were achieved in moderate to good yields.

15.
J Fungi (Basel) ; 10(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38392808

RESUMO

The symbiosis between endophytic fungi and plants can promote the absorption of potassium, nitrogen, phosphorus, and other nutrients by plants. Phosphorus is one of the indispensable nutrient elements for plant growth and development. However, the content of available phosphorus in soil is very low, which limits the growth of plants. Phosphorus-soluble microorganisms can improve the utilization rate of insoluble phosphorus. In this study, Talaromyces verruculosus (T. verruculosus), a potential phosphorus-soluble fungus, was isolated from Acer truncatum, a plant with strong stress resistance, and its phosphorus-soluble ability in relation to cucumber seedlings under different treatment conditions was determined. In addition, the morphological, physiological, and biochemical indexes of the cucumber seedlings were assessed. The results show that T. verruculosus could solubilize tricalcium phosphate (TCP) and lecithin, and the solubilization effect of lecithin was higher than that of TCP. After the application of T. verruclosus, the leaf photosynthetic index increased significantly. The photosynthetic system damage caused by low phosphorus stress was alleviated, and the root morphological indexes of cucumber seedlings were increased. The plant height, stem diameter, and leaf area of cucumber seedlings treated with T. verruculosus were also significantly higher than those without treatment. Therefore, it was shown that T. verruculosus is a beneficial endophytic fungus that can promote plant growth and improve plant stress resistance. This study will provide a useful reference for further research on endophytic fungi to promote growth and improve plant stress resistance.

16.
Sci Total Environ ; 921: 170624, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38325458

RESUMO

Phosphorus (P) is a primary pollutant that builds-up on urban road surfaces. Understanding the fraction and load characteristics of P, as well as their relationship with urban factors, is helpful for assessing the ecological risk of urban receiving water bodies. This study presents the characteristics of build-up loads of P fractions in road-deposited sediments (RDS) in Guangzhou, China, analyzes their correlation with three urban factors (road, traffic, and land-use area), and then estimates the exceedance probability of P in stormwater runoff over the past 10 years. The results showed that detrital apatite phosphorus (De-P) performed the highest build-up load on urban road surfaces, followed by apatite phosphorus (Ca-P), iron-bound phosphorus (Fe-P), exchangeable phosphorus (Ex-P), aluminum-bound phosphorus (Al-P), organophosphorus (POP), dissolved inorganic phosphorus (DIP), occluded phosphorus (Oc-P), and dissolved organic phosphorus (DOP). Depression depth, road materials, and land-use fractions affected the P fractions. The P in the RDS may have originated from three distinct sources: road background, domestic waste, and untreated wastewater discharge. In the most recent 10 years, the event mean concentrations of total P in the RDS have had a 30 % probability of exceeding 0.4 mg L-1, which indicates a serious threat of P to receiving water bodies. The outcomes of this study are expected to provide valuable guidance for elucidating the principal categories of urban non-point source P pollution and enhancing the ecological health of urban water environments.

17.
Colloids Surf B Biointerfaces ; 238: 113928, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692175

RESUMO

In this research, four water-insoluble flavonoid compounds were utilized and reacted with arginine to prepare four carbonized polymer dots with good water-solubility in a hydrothermal reactor. Structural characterization demonstrated that the prepared carbonized polymer dots were classic core-shell structure. Effect of the prepared carbonized polymer dots on protein amyloid aggregation was further investigated using hen egg white lysozyme and human lysozyme as model protein in aqueous solution. All of the prepared carbonized polymer dots could retard the amyloid aggregation of hen egg white lysozyme and human lysozyme in a dose-depended manner. All measurements displayed that the inhibition ratio of luteolin-derived carbonized polymer dots (CPDs-1) was higher than that of the other three carbonized polymer dots under the same dosage. This result may be interpreted by the highest content of phenolic hydroxyl groups on the periphery. The inhibition ratio of CPDs-1 on hen egg white lysozyme and human lysozyme reached 88 % and 83 % at the concentration of 0.5 mg/mL, respectively. CPDs-1 also could disaggregate the formed mature amyloid fibrils into short aggregates.


Assuntos
Amiloide , Flavonoides , Muramidase , Polímeros , Agregados Proteicos , Muramidase/química , Muramidase/metabolismo , Humanos , Polímeros/química , Polímeros/farmacologia , Amiloide/química , Amiloide/antagonistas & inibidores , Flavonoides/química , Flavonoides/farmacologia , Agregados Proteicos/efeitos dos fármacos , Animais , Galinhas , Carbono/química
18.
Eur J Pharmacol ; 962: 176252, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38061470

RESUMO

Vascular remodeling is the pathogenic basis of hypertension and end organ injury, and the proliferation of vascular smooth muscle cells (VSMCs) is central to vascular remodeling. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key effectors of the Hippo pathway and crucial for controlling cell proliferation, apoptosis and differentiation. The present study investigated the role of YAP/TAZ in cardiac and vascular remodeling of angiotensin II-induced hypertension. Ang II induced YAP/TAZ activation in the heart and aorta, which was prevented by YAP/TAZ inhibitor verteporfin. Treatment with verteporfin significantly reduced Ang II-induced cardiac and vascular hypertrophy with a mild reduction in systolic blood pressure (SBP), verteporfin attenuated Ang II-induced cardiac and aortic fibrosis with the inhibition of transform growth factor (TGF)ß/Smad2/3 fibrotic signaling and extracellular matrix collagen I deposition. Ang II induced Rho A, extracellular signal-regulated kinase 1/2 (ERK1/2) and YAP/TAZ activation in VSMCs, either Rho kinase inhibitor fasudil or ERK inhibitor PD98059 suppressed Ang II-induced YAP/TAZ activation, cell proliferation and fibrosis of VSMCs. Verteporfin also inhibited Ang II-induced VSMC proliferation and fibrotic TGFß1/Smad2/3 pathway. These results demonstrate that Ang II activates YAP/TAZ via Rho kinase/ERK1/2 pathway in VSMCs, which may contribute to cardiac and vascular remodeling in hypertension. Our results suggest that YAP/TAZ plays a critical role in the pathogenesis of hypertension and end organ damage, and targeting the YAP/TAZ pathway may be a new strategy for the prevention and treatment of hypertension and cardiovascular diseases.


Assuntos
Hipertensão , Proteínas de Sinalização YAP , Humanos , Quinases Associadas a rho , Angiotensina II/metabolismo , Verteporfina/farmacologia , Remodelação Vascular , Fatores de Transcrição/metabolismo , Hipertensão/tratamento farmacológico , Fibrose
19.
Artigo em Inglês | MEDLINE | ID: mdl-38587576

RESUMO

BACKGROUND: The immediate impact of catheter ablation on left atrial mechanical function and the timeline for its recovery in patients undergoing ablation for atrial fibrillation (AF) remain uncertain. The mechanical function response to catheter ablation in patients with different AF types is poorly understood. METHODS: A total of 113 AF patients were included in this retrospective study. Each patient had three magnetic resonance imaging (MRI) studies in sinus rhythm: one pre-ablation, one immediate post-ablation (within 2 days after ablation), and one post-ablation follow-up MRI (≤ 3 months). We used feature tracking in the MRI cine images to determine peak longitudinal atrial strain (PLAS). We evaluated the change in strain from pre-ablation, immediately after ablation to post-ablation follow-up in a short-term study (< 50 days) and a 3-month study (3 months after ablation). RESULTS: The PLAS exhibited a notable reduction immediately after ablation, compared to both pre-ablation levels and those observed in follow-up studies conducted at short-term (11.1 ± 9.0 days) and 3-month (69.6 ± 39.6 days) intervals. However, there was no difference between follow-up and pre-ablation PLAS. The PLAS returned to 95% pre-ablation level within 10 days. Paroxysmal AF patients had significantly higher pre-ablation PLAS than persistent AF patients in pre-ablation MRIs. Both type AF patients had significantly lower immediate post-ablation PLAS compared with pre-ablation and post-ablation PLAS. CONCLUSION: The present study suggested a significant drop in PLAS immediately after ablation. Left atrial mechanical function recovered within 10 days after ablation. The drop in PLAS did not show a substantial difference between paroxysmal and persistent AF patients.

20.
J Hazard Mater ; 473: 134691, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38788584

RESUMO

Soot nanoparticles (SNPs) are black carbon prevalent in atmospheric environment with significant impacts on public health, leading to neurodegenerative diseases including development of Parkinson's disease (PD). This study investigated the effects of SNPs exposure on PD symptoms, employing both in vivo and in vitro PD models. In the in vivo experiments, animal behavior assessments showed that SNPs exposure exacerbated motor and cognitive impairments in PD mice. Molecular biology techniques further unveiled that SNPs aggravated degeneration of dopaminergic neurons. In vitro experiments revealed that SNPs exposure intensified ferroptosis of PD cells by increasing reactive oxygen species and iron ion levels, while reducing glutathione levels and mitochondrial membrane potential. Sequencing tests indicated elevated N6-methyladenosine (m6A) alteration of the ferroptosis-related protein, acyl-CoA synthetase long chain family member 4 (ACSL4). This study demonstrates that SNPs may exacerbate the onset and progression of PD by recruiting YTH domain-containing family protein 1 (YTHDF1) protein, enhancing m6A methylation in the ACSL4 5'UTR, amplifying ACSL4 protein expression, and accelerating the ferroptosis process in dopaminergic neurons. These molecular mechanisms underlying SNPs exacerbation of PD development may provide crucial insights for formulating environmental safety regulations and potential therapeutic strategies addressing PD in populations residing in regions with varied air quality.


Assuntos
Adenosina , Neurônios Dopaminérgicos , Ferroptose , Camundongos Endogâmicos C57BL , Nanopartículas , Doença de Parkinson , Animais , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Ferroptose/efeitos dos fármacos , Adenosina/análogos & derivados , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Nanopartículas/toxicidade , Nanopartículas/química , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Humanos , RNA , Metilação de RNA
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