Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 72
Filtrar
1.
Cell Mol Life Sci ; 81(1): 164, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575795

RESUMO

Diabetic hyperglycemia induces dysfunctions of arterial smooth muscle, leading to diabetic vascular complications. The CaV1.2 calcium channel is one primary pathway for Ca2+ influx, which initiates vasoconstriction. However, the long-term regulation mechanism(s) for vascular CaV1.2 functions under hyperglycemic condition remains unknown. Here, Sprague-Dawley rats fed with high-fat diet in combination with low dose streptozotocin and Goto-Kakizaki (GK) rats were used as diabetic models. Isolated mesenteric arteries (MAs) and vascular smooth muscle cells (VSMCs) from rat models were used to assess K+-induced arterial constriction and CaV1.2 channel functions using vascular myograph and whole-cell patch clamp, respectively. K+-induced vasoconstriction is persistently enhanced in the MAs from diabetic rats, and CaV1.2 alternative spliced exon 9* is increased, while exon 33 is decreased in rat diabetic arteries. Furthermore, CaV1.2 channels exhibit hyperpolarized current-voltage and activation curve in VSMCs from diabetic rats, which facilitates the channel function. Unexpectedly, the application of glycated serum (GS), mimicking advanced glycation end-products (AGEs), but not glucose, downregulates the expression of the splicing factor Rbfox1 in VSMCs. Moreover, GS application or Rbfox1 knockdown dynamically regulates alternative exons 9* and 33, leading to facilitated functions of CaV1.2 channels in VSMCs and MAs. Notably, GS increases K+-induced intracellular calcium concentration of VSMCs and the vasoconstriction of MAs. These results reveal that AGEs, not glucose, long-termly regulates CaV1.2 alternative splicing events by decreasing Rbfox1 expression, thereby enhancing channel functions and increasing vasoconstriction under diabetic hyperglycemia. This study identifies the specific molecular mechanism for enhanced vasoconstriction under hyperglycemia, providing a potential target for managing diabetic vascular complications.


Assuntos
Diabetes Mellitus Experimental , Angiopatias Diabéticas , Hiperglicemia , Animais , Ratos , Cálcio/metabolismo , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/metabolismo , Constrição , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Angiopatias Diabéticas/metabolismo , Glucose/metabolismo , Hiperglicemia/genética , Hiperglicemia/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Ratos Sprague-Dawley
2.
Zookeys ; 1193: 171-179, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487667

RESUMO

A new species of pholcid spiders, Pholcusfengmeii Zhang, He & Yao, sp. nov. (♂♀), is described from Liaoning Province, China. The new species belongs to the speciose phungiformes species group. Taxonomic keys to four closely related species are provided.

3.
Nat Commun ; 15(1): 1010, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38307902

RESUMO

The reaction system of hydrogen peroxide (H2O2) catalyzed by nanozyme has a broad prospect in antibacterial treatment. However, the complex catalytic activities of nanozymes lead to multiple pathways reacting in parallel, causing uncertain antibacterial results. New approach to effectively regulate the multiple catalytic activities of nanozyme is in urgent need. Herein, Cu single site is modified on nanoceria with various catalytic activities, such as peroxidase-like activity (POD) and hydroxyl radical antioxidant capacity (HORAC). Benefiting from the interaction between coordinated Cu and CeO2 substrate, POD is enhanced while HORAC is inhibited, which is further confirmed by density functional theory (DFT) calculations. Cu-CeO2 + H2O2 system shows good antibacterial properties both in vitro and in vivo. In this work, the strategy based on the interaction between coordinated metal and carrier provides a general clue for optimizing the complex activities of nanozymes.


Assuntos
Antioxidantes , Oxidantes , Antioxidantes/farmacologia , Cobre , Peróxido de Hidrogênio , Radical Hidroxila , Antibacterianos/farmacologia , Peroxidase
4.
Plant J ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308390

RESUMO

Salicylic acid (SA) is known to enhance salt tolerance in plants. However, the mechanism of SA-mediated response to high salinity in halophyte remains unclear. Using electrophysiological and molecular biological methods, we investigated the role of SA in response to high salinity in mangrove species, Kandelia obovata, a typical halophyte. Exposure of K. obovata roots to high salinity resulted in a rapid increase in endogenous SA produced by phenylalanine ammonia lyase pathway. The application of exogenous SA improved the salt tolerance of K. obovata, which depended on the NADPH oxidase-mediated H2 O2 . Exogenous SA and H2 O2 increased Na+ efflux and reduced K+ loss by regulating the transcription levels of Na+ and K+ transport-related genes, thus reducing the Na+ /K+ ratio in the salt-treated K. obovata roots. In addition, exogenous SA-enhanced antioxidant enzyme activity and its transcripts, and the expressions of four genes related to AsA-GSH cycle as well, then alleviated oxidative damages in the salt-treated K. obovata roots. However, the above effects of SA could be reversed by diphenyleneiodonium chloride (the NADPH oxidase inhibitor) and paclobutrazol (a SA biosynthesis inhibitor). Collectively, our results demonstrated that SA-induced salt tolerance of K. obovata depends on NADPH oxidase-generated H2 O2 that affects Na+ /K+ and redox homeostasis in response to high salinity.

5.
J Exp Bot ; 75(8): 2266-2279, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38190348

RESUMO

In plants, C-to-U RNA editing mainly occurs in plastid and mitochondrial transcripts, which contributes to a complex transcriptional regulatory network. More evidence reveals that RNA editing plays critical roles in plant growth and development. However, accurate detection of RNA editing sites using transcriptome sequencing data alone is still challenging. In the present study, we develop PlantC2U, which is a convolutional neural network, to predict plastid C-to-U RNA editing based on the genomic sequence. PlantC2U achieves >95% sensitivity and 99% specificity, which outperforms the PREPACT tool, random forests, and support vector machines. PlantC2U not only further checks RNA editing sites from transcriptome data to reduce possible false positives, but also assesses the effect of different mutations on C-to-U RNA editing based on the flanking sequences. Moreover, we found the patterns of tissue-specific RNA editing in the mangrove plant Kandelia obovata, and observed reduced C-to-U RNA editing rates in the cold stress response of K. obovata, suggesting their potential regulatory roles in plant stress adaptation. In addition, we present RNAeditDB, available online at https://jasonxu.shinyapps.io/RNAeditDB/. Together, PlantC2U and RNAeditDB will help researchers explore the RNA editing events in plants and thus will be of broad utility for the plant research community.


Assuntos
Aprendizado Profundo , Edição de RNA , Edição de RNA/genética , Plantas/metabolismo , Plastídeos/genética , Plastídeos/metabolismo , Transcriptoma , RNA de Plantas/genética , RNA de Plantas/metabolismo
6.
Plant Cell Environ ; 47(3): 832-853, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37984066

RESUMO

Aquaporins (AQPs) regulate the transport of water and other substrates, aiding plants in adapting to stressful environments. However, the knowledge of AQPs in salt-secreting and viviparous Avicennia marina is limited. In this study, 46 AmAQPs were identified in A. marina genome, and their subcellular localisation and function in transporting H2 O2 and boron were assessed through bioinformatics analysis and yeast transformation. Through analysing their expression patterns via RNAseq and real-time quantitative polymerase chain reaction, we found that most AmAQPs were downregulated in response to salt and tidal flooding. AmPIP (1;1, 1;7, 2;8, 2;9) and AmTIP (1;5, 1;6) as salt-tolerant candidate genes may contribute to salt secretion together with Na+ /H+ antiporters. AmPIP2;1 and AmTIP1;5 were upregulated during tidal flooding and may be regulated by anaerobic-responsive element and ethylene-responsive element cis-elements, aiding in adaptation to tidal inundation. Additionally, we found that the loss of the seed desiccation and dormancy-related TIP3 gene, and the loss of the seed dormancy regulator DOG1 gene, or DOG1 protein lack heme-binding capacity, may be genetic factors contributing to vivipary. Our findings shed light on the role of AQPs in A. marina adaptation to intertidal environments and their relevance to salt secretion and vivipary.


Assuntos
Aquaporinas , Avicennia , Avicennia/metabolismo , Ecossistema , Água/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-38041777

RESUMO

Intestinal fibrosis is a common complication of inflammatory bowel disease and is characterized by tissue stiffening and luminal narrowing. Dihydromyricetin (DHM) can alleviate liver fibrosis and renal interstitial fibrosis by inducing autophagy. However, whether DHM can alleviate intestinal fibrosis remains unclear. This study is aimed at evaluating the role and mechanism of action of DHM in inflammatory bowel disease-associated intestinal fibrosis. Mice were administered dextran sulfate sodium (DSS) in drinking water to induce inflammatory bowel disease-associated intestinal fibrosis. HE staining, qPCR, and Western blotting were used to analyze colon inflammation. Masson's trichrome staining, qPCR, Western blotting, and immunofluorescence staining were used to evaluate the severity of fibrosis. Transmission electron microscopy and Western blotting were used to assess the activation of autophagosomes. The human colonic fibroblast line CCD-18Co was cultured in the presence of TGF-ß1 to develop a fibrotic phenotype. Immunofluorescence staining, Western blotting, and qPCR were used to assess the alteration of fibrosis markers and used to investigate whether DHM-induced autophagy was involved in the inactivation of CCD-18Co cells. Additionally, the role of the PI3K/AKT/mTOR pathway was investigated. DHM alleviated intestinal inflammation and inhibited the progression of intestinal fibrosis. Additionally, DHM induced the activation of autophagy, thereby alleviating intestinal fibrosis, and downregulated the PI3K/AKT/mTOR signaling pathway in vitro. Overall, this study demonstrated that DHM can inhibit the progression of intestinal fibrosis and activation of colonic fibroblasts by inducing autophagy through the PI3K/AKT/mTOR signaling pathway, thereby playing a preventive and therapeutic role in intestinal fibrosis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38083266

RESUMO

Autism has become one of the primary diseases causing disability in children, and the incidence has risen rapidly in recent years. The preclinical study on individuals with high autistic traits is extremely important to reduce genetic risks of autism because high autistic traits is the susceptibility marker of autism. However, few studies explored the face scanning pattern of people with high autistic traits in typical developing populations. In this study, we designed a facial emotion recognition experiment including four emotions (happy, neutral, sad, angry) and three angles (0°, 45°, 90°) , and informed the participants to identify the facial emotion. Forty-two college students with typical development were recruited and divided into high autistic traits (HAT) group and low autistic traits (LAT) group by the Autism-Spectrum Quotient, and we collected the eye movement data using eye-tracking technology when they performed the task. The response time, recognition accuracy, AOI based proportional fixation time and pupil diameter were computed and analyzed for both groups. HATs showed significantly lower recognition accuracy and lower pupil diameter than LATs when recognizing negative emotions (P<0.05) , indicating HATs kept poor autonomic nervous arousal. What ' s more, the proportional fixation time of HATs were significantly more in mouth area but less in eye area than that of LAT group (P<0.05) , revealed HATs had an atypical emotional faces scanning strategies that paid less attention to eyes and more attention to mouth. Our research provides a feasible objective biomarker for screening high autistic traits population.


Assuntos
Transtorno Autístico , Criança , Humanos , Transtorno Autístico/diagnóstico , Expressão Facial , Emoções/fisiologia , Felicidade , Movimentos Oculares
9.
iScience ; 26(12): 108494, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38125016

RESUMO

Aneuploidy can globally affect the expression of the whole genome, which is detrimental to organisms. Dosage-sensitive regulators usually have multiple intermolecular interactions, and changes in their stoichiometry are responsible for the dysregulation of the regulatory network. Currently, studies on noncoding genes in aneuploidy are relatively rare. We studied the characteristics and expression profiles of long noncoding RNAs (lncRNAs) and transposable elements (TEs) in aneuploid Drosophila. It is found that lncRNAs and TEs are affected by genomic imbalance and appear to be more sensitive to an inverse dosage effect than mRNAs. Several dosage-sensitive lncRNAs and TEs were detected for their expression patterns during embryogenesis, and their biological functions in the ovary and testes were investigated using tissue-specific RNAi. This study advances our understanding of the noncoding sequences in imbalanced genomes and provides a novel perspective for the study of aneuploidy-related human diseases such as cancer.

10.
J Hazard Mater ; 459: 132321, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37597395

RESUMO

Mangrove Avicennia marina has the importantly potential for cadmium (Cd) pollution remediation in coastal wetlands. Unfortunately, the molecular mechanisms and transporter members for Cd uptake by the roots of A. marina are not well documented. In this study, photosynthetic and phenotypic analysis indicated that A. marina is particularly tolerant to Cd. The content and flux analysis indicated that Cd is mainly retained in the roots, with greater Cd influx in fine roots than that in coarse roots, and higher Cd influx in the root meristem zone as well. Using transcriptomic analysis, a total of 5238 differentially expressed genes were identified between the Cd treatment and control group. Moreover, we found that 54 genes were responsible for inorganic ion transport. Among these genes, AmHMA2, AmIRT1, and AmPCR2 were localized in the plasma membrane and AmZIP1 was localized in both plasma membrane and cytoplasm. All above gene encoding transporters showed significant Cd transport activities using function assay in yeast cells. In addition, the overexpression of AmZIP1 or AmPCR2 in Arabidopsis improved the Cd tolerance of transgenic plants. This is particularly significant as it provides insight into the molecular mechanism for Cd uptake by the roots of mangrove plants and a theoretical basis for coastal wetland phytoremediation.


Assuntos
Arabidopsis , Avicennia , Fabaceae , Avicennia/genética , Cádmio/toxicidade , Proteínas de Membrana Transportadoras , Transporte Biológico , Áreas Alagadas
11.
Environ Sci Pollut Res Int ; 30(42): 96001-96018, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37561303

RESUMO

Floods are one of the most frequent global natural hazards resulting in significant human and economic losses. Therefore, assessing and mapping flood hazard levels is essential to reduce the severity of future flood disasters. This study developed an integrated methodology to evaluate flood risk using an improved Analytic Hierarchy Process (AHP) and Entropy Weight (AHP-EW) method based on cosine similarity (COS-AHP-EW). This method has more scientific results because it combines subjective and objective information. The proposed method's viability was then tested in Wuhan, China. Fourteen flood-inducing indicators were identified for the flood hazard, vulnerability, and restorability index system, with the indicator weights calculated using the COS-AHP-EW. This study utilized the Jenks method to develop the Wuhan flood risk map. We observed that the very high risk and high-risk areas covered 2.43% and 11.54% of the total study area and were mainly distributed in the highest economic and urbanization development and low-permeability districts, respectively. The validation with the historical waterlogging points reflected the accuracy and reliability of the COS-AHP-EW. The superiority of the proposed method was further verified by comparing it with single-evaluation methods (AHP and Entropy Weight) and another combined weight method (combined AHP-EW based on ideal point theory, namely, Ideal-AHP-EW). The comparison results indicated that the COS-AHP-EW was more accurate at predicting the risk in flood-prone area. Flood risk maps generated using the COS-AHP-EW could be applied to improve flood risk assessments, and the proposed method could be extended to other study areas to provide reliable flood management information.


Assuntos
Processo de Hierarquia Analítica , Inundações , Humanos , Entropia , Reprodutibilidade dos Testes , China , Medição de Risco
12.
Inorg Chem ; 62(30): 11876-11886, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37449705

RESUMO

New solid electrolytes are crucial for the development of all-solid-state lithium batteries with advantages in safety and energy densities over current liquid electrolyte systems. While some of the best solid-state Li+-ion conductors are based on sulfides, their air sensitivity makes them less commercially attractive, and attention is refocusing on air-stable oxide-based systems. Among these, the LISICON-structured systems, such as Li2+2xZn1-xGeO4 and Li3+xV1-xGexO4, have been relatively well studied. However, other systems such as the Li4GeO4-Li2MoO4 system, which also show LISICON-type structures, have been relatively little explored. In this work, the Li4-2xGe1-xMoxO4 solid solution is investigated systematically, including the solid solution limit, structural stability, local structure, and the corresponding electrical behavior. It is found that a γ-LISICON structured solution is formed in the range of 0.1 ≤ x < 0.4, differing in structure from the two end members, Li4GeO4 and Li2MoO4. With increasing Mo content, the ß-phase becomes increasingly more stable than the γ-phase, and at x = 0.5, a pure ß-phase (ß-Li3Ge0.5Mo0.5O4) is readily isolated. The structure of this previously unknown compound is presented, along with details of the defect structure of Li3.6Ge0.8Mo0.2O4 (x = 0.2) based on neutron diffraction data. Two basic types of defects are identified in Li3.6Ge0.8Mo0.2O4 involving interstitial Li+-ions in octahedral sites, with evidence for these coming together to form larger defect clusters. The x = 0.2 composition shows the highest conductivity of the series, with values of 1.11 × 10-7 S cm-1 at room temperature rising to 5.02 × 10-3 S cm-1 at 250 °C.

13.
Adv Mater ; 35(46): e2305077, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37497609

RESUMO

Recently, single-atom nanozymes have made significant progress in the fields of sterilization and treatment, but their catalytic performance as substitutes for natural enzymes and drugs is far from satisfactory. Here, a method is reported to improve enzyme activity by adjusting the spatial position of a single-atom site on the nanoplatforms. Two types of Cu single-atom site nanozymes are synthesized in the interlayer (CuL /PHI) and in-plane (CuP /PHI) of poly (heptazine imide) (PHI) through different synthesis pathways. Experimental and theoretical analysis indicates that the interlayer position of PHI can effectively adjust the coordination number, coordination bond length, and electronic structure of Cu single atoms compared to the in-plane position, thereby promoting photoinduced electron migration and O2 activation, enabling effective generate reactive oxygen species (ROS). Under visible light irradiation, the photocatalytic bactericidal activity of CuL /PHI against aureus is ≈100%, achieving the same antibacterial effect as antibiotics, after 10 min of low-dose light exposure and 2 h of incubation.


Assuntos
Antibacterianos , Eletrônica , Antibacterianos/farmacologia , Catálise , Elétrons , Imidas
14.
Plant Cell Rep ; 42(9): 1473-1485, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37516984

RESUMO

KEY MESSAGE: This study provided important insights into the genetic architecture of variations in A. thaliana leaf ionome in a cell-type-specific manner. The functional interpretation of traits associated variants by expression quantitative trait loci (eQTL) analysis is usually performed in bulk tissue samples. While the regulation of gene expression is context-dependent, such as cell-type-specific manner. In this study, we estimated cell-type abundances from 728 bulk tissue samples using single-cell RNA-sequencing dataset, and performed cis-eQTL mapping to identify cell-type-interaction eQTL (cis-eQTLs(ci)) in A. thaliana. Also, we performed Genome-wide association studies (GWAS) analyses for 999 accessions to identify the genetic basis of variations in A. thaliana leaf ionome. As a result, a total of 5,664 unique eQTL genes and 15,038 unique cis-eQTLs(ci) were significant. The majority (62.83%) of cis-eQTLs(ci) were cell-type-specific eQTLs. Using colocalization, we uncovered one interested gene AT2G25590 in Phloem cell, encoding a kind of plant Tudor-like protein with possible chromatin-associated functions, which colocalized with the most significant cis-eQTL(ci) of a Mo-related locus (Chr2:10,908,806:A:C; P = 3.27 × 10-27). Furthermore, we prioritized eight target genes associated with AT2G25590, which were previously reported in regulating the concentration of Mo element in A. thaliana. This study revealed the genetic regulation of ionomic variations and provided a foundation for further studies on molecular mechanisms of genetic variants controlling the A. thaliana ionome.


Assuntos
Arabidopsis , Locos de Características Quantitativas , Arabidopsis/genética , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética
15.
Wei Sheng Yan Jiu ; 52(3): 434-439, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37500524

RESUMO

OBJECTIVE: To explore the feasibility of applying graphical menu labeling. METHODS: To design a radar chart menu label. From October 2020 to April 2021, convenience sampling was adopted to recruit 1407 research subjects(986 females and 421 males) through the online platform nationwide to complete the questionnaire and simulate ordering. The survey included basic information of the research subjects, their level of nutritional knowledge, and satisfaction with the graphic menu labels. The two simulated orderings were conducted using the regular menu and the menu with graphic nutritional information, respectively. Compare the nutrition scores of the two simulated orders, the selection ratio of each dish in each major category, the energy, fat, cholesterol and sodium content, and the amount of added oil and salt of the selected dishes. RESULTS: Compared with using the normal menu, the nutritional score of the simulated meal ordering increased from 15.57±2.65 to 16.73±3.24(P<0.05) using a menu with graphic nutrition labels, in which people with an income of less than 4000 yuan and a graduate degree or above increased the most. The proportion of dishes with higher nutritional value has increased among pork, fish, vegetables, and soy products. The energy, fat, cholesterol, sodium content, added oil and added salt of the selected dishes are decreased from 8455(7738, 9033) kcal, 658.6(598.1, 709.3) g, 1418(1238, 1665) mg, 17 430(15 695, 19 129)mg, 455(405, 502)g, 41.5(36.5, 47.0)g to 7415(6693, 8191)kcal, 562.54(504.0, 631.2)g, 1274(1076, 1549)mg, 17 185(14 574, 19 576.8)mg, 375(334, 437) g, 38.5(32.4, 43.6) g respectively(P<0.05). The satisfaction score of the graphic nutrition label is relatively high. CONCLUSION: Graphical menu labeling helps consumers to make healthier choices for catering food.


Assuntos
Ingestão de Energia , Restaurantes , Animais , Estado Nutricional , Valor Nutritivo , Verduras , Sódio , Cloreto de Sódio na Dieta , Rotulagem de Alimentos
16.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2010-2019, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282891

RESUMO

Chronic heart failure(CHF) has become a worldwide public health problem due to its high morbidity and mortality, which seriously endangers people's lifespan and quality of life. In recent years, the treatment strategy of CHF has shifted its emphasis on short-term improvement and transformation of hemodynamics to long-term repair as well as improvement of the biological properties of heart failure. At present, with the continuous deepening of medical research, it has been found that histone acetylation is closely related to the occurrence and development of CHF. Traditional Chinese medicine, via regulating histone acetylation, delays ventricular remodeling, improves energy metabolism, inhibits fibrosis and cardiomyocyte hypertrophy, and intervenes in the development process of heart failure, thus reducing the mortality and the readmission rate and ultimately improving long-term prognosis. Therefore, this study reviewed the mechanism of histone acetylation in the treatment of heart failure as well as its prevention and treatment with traditional Chinese medicine, to provide reference for clinical treatment of CHF.


Assuntos
Insuficiência Cardíaca , Medicina Tradicional Chinesa , Humanos , Histonas/metabolismo , Histonas/uso terapêutico , Acetilação , Qualidade de Vida , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle
17.
Theranostics ; 13(9): 2787-2799, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37284444

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology with no cure. A better understanding of the disease processes and identification of druggable targets will benefit the development of effective therapies for IPF. We previously reported that MDM4 promoted lung fibrosis through the MDM4-p53-dependent pathway. However, it remained unclear whether targeting this pathway would have any therapeutic potential. In this study, we evaluated the efficacy of XI-011, a small molecular inhibitor of MDM4, for treating lung fibrosis. We found that XI-011 significantly reduced MDM4 expression and increased the expression of total and acetylated p53 in primary human myofibroblasts and a murine fibrotic model. XI-011 treatment resulted in the resolution of lung fibrosis in mice with no notable impact on normal fibroblast death or the morphology of healthy lungs. Based on these findings, we propose that XI-011 might be a promising therapeutic drug candidate for treating pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática , Proteína Supressora de Tumor p53 , Humanos , Camundongos , Animais , Proteína Supressora de Tumor p53/metabolismo , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Antracenos/farmacologia , Pulmão/metabolismo , Fibroblastos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas de Ciclo Celular/metabolismo
18.
Nanomedicine (Lond) ; 18(9): 755-767, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37306248

RESUMO

Aim: STING agonists in immunotherapy show great promise and are currently in clinical trials. Combinations of STING agonists with other therapies remain underexplored. This study aimed to combine STING agonist-mediated immunotherapy with photodynamic therapy to treat breast cancer. Methods: STING agonist (ADU-S100)-functionalized porphyrin-based nanoparticles (NP-AS) were prepared and their antitumor properties in terms of cell apoptosis/necrosis and immune activation in triple-negative breast cancer were evaluated. Results: NP-AS induced tumor cell apoptosis/necrosis, activated the innate immune response and exhibited useful antitumor effects. Conclusion: NP-AS effectively treated breast cancer.


Assuntos
Nanopartículas , Neoplasias , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Imunoterapia , Necrose , Neoplasias/terapia
19.
J Psycholinguist Res ; 52(5): 1571-1587, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37148448

RESUMO

In modern media, the names of fairy-tale and mythological images are used to convey certain emotions and connotations. The aim of the study is to analyze the characteristic associative strategies presented with the mythological images of a dragon, a paper tiger and a chimera in news texts of European and Chinese mass media. In this article, the method of text analysis was used to identify patterns and the most possible interpretations of lexical units. 100 articles from Chinese and European publications were selected for the analysis (About People's Daily Online, China News Service, Guardian and France 24). The required lexemes were most widely used in articles on political topics. The most used was the image of a paper tiger (4001 and 3587 units). This is due to its well-known metaphorical meaning in both cultures, while dragon differs in Chinese and European ones. Further research may focus on the search and analysis of other fairy tale and mythological images in mass media. The present study results may also be applied for further research in the field of linguistics and journalism.


Assuntos
Comunicação , Fala , Humanos , Linguística , Idioma , Cognição
20.
Front Psychiatry ; 14: 1086282, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37032943

RESUMO

Introduction: Reduced fixation to the eye area is the main characteristic of social deficits associated with Autism Spectrum Disorder; a similar pattern may exist in individuals with high autistic traits. However, their scanning patterns to the eye area of emotional faces are still unclear on the time scale. Methods: In the present study, we recruited 46 participants and divided them into the high autistic traits (HAT) group (23 participants) and the low autistic traits (LAT) group (20 participants) based on their Autism Spectrum Quotient (AQ) scores. Moreover, we captured their eye movement patterns when observing different angular emotional faces. We extracted the proportional fixation time to the eye area under different time windows. Results: The results showed that the fixation time of the HAT group was always significantly smaller than that of the LAT group (p < 0.05), and the difference between the two groups increased in the middle and late stages of face presentation. The results of the linear regression analysis showed that the proportional fixation time was negatively correlated with AQ scores (p < 0.05), indicating that the proportional fixation time to the eye area could be a potential indicator to measure the level of autistic traits. We then calculated the latency to orient the eye area and the latency to disengage the eye area to explore the priority of observation of the eyes. The results showed that compared with the LAT group, the HAT group has a longer latency to orient the eye area (p < 0.05) and has longer latency to disengage the eye area (p < 0.05), illustrating that the HAT group saw the eyes more slowly and left them faster.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...