Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
1.
ACS Appl Mater Interfaces ; 16(25): 32702-32712, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38870327

RESUMO

Herein, we report a dual-functional flexible sensor (DFFS) using a magnetic conductive polymer composed of nickel (Ni), carbon black (CB), and polydimethylsiloxane (PDMS). The material selection for the DFFS utilizes the excellent elasticity of the PDMS matrix and the synergistic interaction between Ni and CB. The DFFS has a wide strain range of 0-170%, a high sensitivity of 74.13 (140-170%), and a low detection limit of 0.3% strain. The DFFS based on superior performance can accurately detect microstrain/microvibration, oncoming/contacting objects, and bicycle riding speed. Additionally, the DFFS can be used for comprehensive monitoring of human movements. Therefore, the DFFS of this work shows significant value for implementation in intelligent wearable devices and noncontact intelligent control.


Assuntos
Dimetilpolisiloxanos , Microesferas , Níquel , Fuligem , Dispositivos Eletrônicos Vestíveis , Dimetilpolisiloxanos/química , Humanos , Níquel/química , Fuligem/química , Movimento , Condutividade Elétrica
2.
Cells ; 13(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38786060

RESUMO

Cells defend against oxidative stress by enhancing antioxidant capacity, including stress-activated metabolic alterations, but the underlying intracellular signaling mechanisms remain unclear. This paper reports that immunoglobulin superfamily containing leucine-rich repeat (ISLR) functions as a redox sensor that responds to reactive oxygen species (ROS) stimulation and modulates the antioxidant capacity by suppressing pyruvate kinase isozyme M2 (PKM2) activity. Following oxidative stress, ISLR perceives ROS stimulation through its cysteine residue 19, and rapidly degrades in the autophagy-lysosome pathway. The downregulated ISLR enhances the antioxidant capacity by promoting the tetramerization of PKM2, and then enhancing the pyruvate kinase activity, PKM2-mediated glycolysis is crucial to the ISLR-mediated antioxidant capacity. In addition, our results demonstrated that, in triple-negative breast cancer, cisplatin treatment reduced the level of ISLR, and PKM2 inhibition sensitizes tumors to cisplatin by enhancing ROS production; and argued that PKM2 inhibition can synergize with cisplatin to limit tumor growth. Our results demonstrate a molecular mechanism by which cells respond to oxidative stress and modulate the redox balance.


Assuntos
Antioxidantes , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio , Humanos , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Cisplatino/farmacologia , Feminino , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Proteínas de Ligação a Hormônio da Tireoide , Camundongos , Piruvato Quinase/metabolismo , Glicólise/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/enzimologia
3.
FASEB J ; 38(7): e23534, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38597911

RESUMO

Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.


Assuntos
Sistema de Sinalização das MAP Quinases , Osteonectina , Animais , Camundongos , Divisão Celular Assimétrica , Diferenciação Celular , Osteonectina/genética , Transdução de Sinais
4.
Artigo em Inglês | MEDLINE | ID: mdl-38657655

RESUMO

An essential factor in tooth nutritional deficits and aberrant root growth is pulp necrosis. Removing inflammatory or necrotic pulp tissue and replacing it with an inert material are the most widely used therapeutic concepts of endodontic treatment. However, pulp loss can lead to discoloration, increased fracture risk, and the reinfection of the damaged tooth. It is now anticipated that the pulp-dentin complex will regenerate through a variety of application methods based on human dental pulp stem cells (hDPSC). In order to create a photo-cross-linked gelatinized methacrylate hydrogel, GelMA/EUO-CDs-E (ECE), that is biodegradable and injectable for application, we created a novel nanoassembly of ECE based on eucommia carbon dots (EUO-CDs) and epigallocatechin gallate (EGCG). We then loaded it onto gelatin methacryloyl (GelMA) hydrogel. We have evaluated the material and examined its in vivo and in vitro angiogenesis-promoting potential as well as its dentin differentiation-enabling characteristics. The outcomes of the experiment demonstrated that GelMA/ECE was favorable to cell proliferation and enhanced hDPSC's capacity for angiogenesis and dentin differentiation. The regeneration of vascular-rich pulp-like tissues was found to occur in vivo when hDPSC-containing GelMA/ECE was injected into cleaned human root segments (RS) for subcutaneous implantation in nude mice. This suggests that the injectable bioscaffold is appropriate for clinical use in pulp regenerative medicine.

5.
Biomed Pharmacother ; 174: 116448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522241

RESUMO

BACKGROUND: The roots and rhizomes of Nardostachys jatamansi DC. are reported to be useful for the treatment of Parkinson's disease (PD). Previous research has also shown that Nardosinone, the main active component isolated from Nardostachys jatamansi DC., exhibits the potential to treat PD. AIM OF THE STUDY: To investigate how the effects of Nardosinone could assist levodopa in the treatment of PD, how this process changes the intestinal flora, and to explore the effective forms of Nardosinone in the intestinal flora. MATERIAL AND METHODS: We used behavioral experiments, and hematoxylin-eosin staining and immunohistochemical staining, to investigate the effects of a combination of Nardosinone and levodopa on rotenone-induced PD rats. In addition, we used LC/MS-MS to determine the levels of levodopa, 5-hydroxytryptamine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, and homovanillic acid, to investigate the effect of the intestinal flora on co-administration in the treatment of PD. LC/MS-MS was also used to detect the metabolites of Nardosinone on the gastrointestinal tract and intestinal flora. RESULTS: The behavioral disorders and neuronal damage associated with PD were significantly improved following the co-administration. Analysis also revealed that the co-administration increased the levels of five neurotransmitters in the striatum, plasma and feces. In vitro experiments further demonstrated that the levels of dopamine and levodopa were increased in the intestinal flora. In total, five metabolites of Nardosinone were identified. CONCLUSION: Our findings indicate that Nardosinone and its metabolites might act as a potential adjutant to enhance the efficacy of levodopa via the intestinal flora, thus expanding the therapeutic potential of the combination of Chinese and Western medicine as a treatment method for PD.


Assuntos
Microbioma Gastrointestinal , Levodopa , Doença de Parkinson , Ratos Sprague-Dawley , Levodopa/farmacologia , Animais , Masculino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Ratos , Microbioma Gastrointestinal/efeitos dos fármacos , Antiparkinsonianos/farmacologia , Rotenona/farmacologia , Nardostachys/química , Dopamina/metabolismo , Comportamento Animal/efeitos dos fármacos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38556538

RESUMO

Rheumatoid arthritis (RA) is a common immune disease characterized mainly by erosive arthritis with extensive clinical sequelae. Resveratrol (Res) has pharmacological effects in the treatment of RA, but it has not been widely used in the clinic due to its poor water solubility and low bioavailability. In this study, a drug delivery system (Res-NC MNs) of dissolved microneedles (MNs) loaded with Res nanocrystals (NC) was designed for the treatment of RA. Res-NC MNs can improve the drawbacks of long-term oral drug delivery with toxic side effects and low compliance associated with intra-articular drug delivery. In this study, Res-NC was prepared by media milling and loaded into soluble microneedles prepared from hyaluronic acid (HA) by vacuum casting for the treatment of RA. HA has high mechanical strength and can penetrate the cuticle layer of the skin for effective drug delivery. In in vivo pharmacodynamic experiments, Res-NC MNs achieved better therapeutic efficacy in the treatment of RA compared with oral Res. These findings suggest that Res-NC MNs may be an effective and promising drug delivery strategy for the treatment of RA.

7.
Cell Prolif ; 57(7): e13612, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38348888

RESUMO

Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1-like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE-Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE-Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis of l-arginine and expression of inducible nitric oxide synthase in OE-Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.


Assuntos
Encefalomielite Autoimune Experimental , Imunomodulação , Células-Tronco Mesenquimais , Metformina , Camundongos Endogâmicos C57BL , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Animais , Metformina/farmacologia , Camundongos , Imunomodulação/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Colite/tratamento farmacológico , Colite/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Reprogramação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Células Cultivadas , Movimento Celular/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/citologia , Reprogramação Metabólica
8.
Comput Methods Biomech Biomed Engin ; 27(3): 296-305, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36939836

RESUMO

OBJECTIVES: To evaluate the biomechanical system of molar distalization with clear aligner therapy (CAT) combined with angel button using interradicular mini-implants (IRMIs) with varying elastic forces. MATERIALS AND METHODS: FE models including maxilla, complete maxillary dentition, periodontal ligaments (PDL), composite attachments, mini-implants (MI), and dedicated orthodontic aligner, were constructed. Three groups were created in accordance with the sagittal position of MI. Elastic forces (0 N,1 N,1.5 N,2 N) were applied. RESULTS: CAT without elastics caused labial tipping and intrusion of the anterior teeth. Initial labial tipping and the von Mises stress of the maxillary anterior teeth decreased as the elastic forces increased.


Assuntos
Aparelhos Ortodônticos Removíveis , Tração , Análise de Elementos Finitos , Dente Molar/cirurgia , Ligamento Periodontal , Maxila/cirurgia , Técnicas de Movimentação Dentária
9.
Plant Cell ; 36(4): 1098-1118, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38092516

RESUMO

DNA methylation is an important epigenetic mark implicated in selective rRNA gene expression, but the DNA methylation readers and effectors remain largely unknown. Here, we report a protein complex that reads DNA methylation to regulate variant-specific 45S ribosomal RNA (rRNA) gene expression in Arabidopsis (Arabidopsis thaliana). The complex, consisting of METHYL-CpG-BINDING DOMAIN PROTEIN5 (MBD5), MBD6, ALPHA-CRYSTALLIN DOMAIN PROTEIN15.5 (ACD15.5), and ACD21.4, directly binds to 45S rDNA. While MBD5 and MBD6 function redundantly, ACD15.5 and ACD21.4 are indispensable for variant-specific rRNA gene expression. These 4 proteins undergo phase separation in vitro and in vivo and are interdependent for their phase separation. The α-crystallin domain of ACD15.5 and ACD21.4, which is essential for their function, enables phase separation of the complex, likely by mediating multivalent protein interactions. The effector MICRORCHIDIA6 directly interacts with ACD15.5 and ACD21.4, but not with MBD5 and MBD6, and is recruited to 45S rDNA by the MBD-ACD complex to regulate variant-specific 45S rRNA expression. Our study reveals a pathway in Arabidopsis through which certain 45S rRNA gene variants are silenced, while others are activated.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , alfa-Cristalinas , Arabidopsis/genética , Arabidopsis/metabolismo , Genes de RNAr , Metilação de DNA/genética , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , DNA Ribossômico/genética , DNA Ribossômico/metabolismo , alfa-Cristalinas/genética , alfa-Cristalinas/metabolismo
10.
Adv Sci (Weinh) ; 10(36): e2303545, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37963851

RESUMO

O-GlcNAcylation functions as a cellular nutrient and stress sensor and participates in almost all cellular processes. However, it remains unclear whether O-GlcNAcylation plays a role in the establishment and maintenance of cell polarity, because mice lacking O-GlcNAc transferase (OGT) are embryonically lethal. Here, a mild Ogt knockout mouse model is constructed and the important role of O-GlcNAcylation in establishing and maintaining cell polarity is demonstrated. Ogt knockout leads to severe pulmonary fibrosis and dramatically promotes epithelial-to-mesenchymal transition. Mechanistic studies reveal that OGT interacts with pericentriolar material 1 (PCM1) and centrosomal protein 131 (CEP131), components of centriolar satellites required for anchoring microtubules to the centrosome. These data further show that O-GlcNAcylation of PCM1 and CEP131 promotes their centrosomal localization through phase separation. Decrease in O-GlcNAcylation prevents PCM1 and CEP131 from localizing to the centrosome, instead dispersing these proteins throughout the cell and impairing the microtubule-centrosome interaction to disrupt centrosome positioning and cell polarity. These findings identify a previously unrecognized role for protein O-GlcNAcylation in establishing and maintaining cell polarity with important implications for the pathogenesis of pulmonary fibrosis.


Assuntos
Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/metabolismo , Polaridade Celular , Centrossomo/metabolismo , Fenótipo
11.
BMC Public Health ; 23(1): 2228, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37953277

RESUMO

INTRODUCTION: Dolutegravir (DTG)-based regimen was included in the expanded formulary of China's National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China. METHODS: A decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis. RESULTS: Compared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses. CONCLUSIONS: DTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Análise de Custo-Efetividade , Didesoxinucleosídeos/efeitos adversos , Lamivudina/efeitos adversos , Antirretrovirais/uso terapêutico , Emtricitabina/uso terapêutico , Benzoxazinas/uso terapêutico
12.
Molecules ; 28(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37375355

RESUMO

In this study, soluble dietary fibers (SDFs) were extracted from rape bee pollen using four methods including acid extraction (AC), alkali extraction (AL), cellulase extraction (CL) and complex enzyme extraction (CE). The effects of different extraction methods on the structure of SDFs and in vitro fermentation characteristics were further investigated. The results showed that the four extraction methods significantly affected the monosaccharide composition molar ratio, molecular weight, surface microstructure and phenolic compounds content, but showed little effect on the typical functional groups and crystal structure. In addition, all SDFs decreased the Firmicutes/Bacteroidota ratio, promoted the growth of beneficial bacteria such as Bacteroides, Parabacteroides and Phascolarctobacterium, inhibited the growth of pathogenic bacteria such as Escherichia-Shigella, and increased the total short-chain fatty acids (SCFAs) concentrations by 1.63-2.45 times, suggesting that the bee pollen SDFs had a positive regulation on gut microbiota. Notably, the SDF obtained by CE exhibited the largest molecular weight, a relatively loose structure, higher extraction yield and phenolic compounds content and the highest SCFA concentration. Overall, our results indicated that CE was an appropriate extraction method of high-quality bee pollen SDF.


Assuntos
Bactérias , Ácidos Graxos Voláteis , Animais , Abelhas , Fermentação , Ácidos Graxos Voláteis/análise , Fenóis/química , Pólen/química , Bacteroidetes , Fibras na Dieta/análise
13.
Int. j. morphol ; 41(3): 889-893, jun. 2023. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1514319

RESUMO

SUMMARY: The objective of this study was to evaluate the changes of head and cervical spine posture of skeletal class malocclusion in adolescent with maxillary protraction. Thirty cases of skeletal class malocclusion were randomly selected from the Stomatological Hospital of Shanxi Medical University. High-quality lateral cephalograms were collected including pre- and posttreatment to compare the changes of head and cervical spine posture. Data were processed using SPSS 26.0 statistical software. The paired-t test was used to compare pre- and posttreatment mean angular measurements.A significant difference in the SNA(p<0.001), SNB(p<0.01), and ANB(p<0.001) between T1 and T2 showed an improvement in the sagittal relationships. A significant change was observed in middle cervical spine posture, while upper cervical spine posture variables showed no significant difference after treatment. Skeletal class with maxillary protraction appliance not only led to the improvement of sagittal relationship, but also changed the middle cervical spine posture.


El objetivo de este estudio fue evaluar los cambios en la postura de la cabeza y la columna cervical debido a la maloclusión clase esquelética en adolescentes con protracción maxilar. Treinta casos de maloclusión de clase esquelética fueron seleccionados al azar del Hospital Estomatológico de la Universidad Médica de Shanxi. Se recogieron cefalogramas laterales de alta calidad, incluidos el tratamiento previo y posterior, para comparar los cambios en la postura de la cabeza y la columna cervical. Los datos se procesaron con el software estadístico SPSS 26.0. Se utilizó la prueba t pareada para comparar las medidas angulares medias antes y después del tratamiento. Una diferencia significativa en SNA (p <0,001), SNB (p <0,01) y ANB (p <0,001) entre T1 y T2 mostró una mejora en las relaciones sagitales. Se observó un cambio significativo en la postura de la columna cervical media, mientras que las variables de postura de la columna cervical superior no mostraron diferencias significativas después del tratamiento. La clase esquelética con aparato de protracción maxilar no solo condujo a la mejora de la relación sagital, sino que también cambió la postura de la columna cervical media.


Assuntos
Humanos , Criança , Postura , Vértebras Cervicais/anatomia & histologia , Cabeça/anatomia & histologia , Má Oclusão Classe III de Angle/terapia , Cefalometria , Pontos de Referência Anatômicos
14.
Artigo em Inglês | MEDLINE | ID: mdl-37159088

RESUMO

The objectives of this study were to evaluate the tooth movement tendency during space closure in maxillary anterior teeth by various combinations of retraction force and intrusive force in a double-archwire lingual orthodontic system. Mini-implant-double slot lingual orthodontics system models of the bilateral maxillary first premolar extraction cases were constructed. Three-dimensional finite element models of the maxilla were constructed with definite position mini-implants (8 mm) and power arms (6 mm). Different retraction forces(50gf、100gf、150gf)were applied with the help of a nickel-titanium closed coil spring on the plate side. Intrusive forces(0gf、50gf、100gf)were applied with the help of the mini-implant between the two central incisors, and the initial displacements of the maxillary anterior teeth were analyzed. Variable amounts of displacements like controlled tipping, uncontrolled tipping, lingual crown tipping, labial root tipping, extrusion and distal crown tipping were observed in all the models, and these tendencies increased as the magnitude of retraction force increased, and these tendencies decreased as the magnitude of intrusive force increased. When the intrusive force was greater than or equal to the retraction force, the maxillary central incisors showed the trend of lingual crown tipping and labial root tipping, resulting in uncontrolled tipping movement. In terms of horizontal changes, the increasing width of bilateral anterior teeth was observed, with canines showing the least increasing trend. Various combinations of retraction force and intrusive force in a double-archwire lingual orthodontic system provide a new choice for torque control of the anterior teeth. Although anterior mini-implants and elastics can achieve incisor intrusion and lingual root torque, they cannot achieve the expected torque without additional torque control methods.

15.
Artigo em Inglês | MEDLINE | ID: mdl-37141056

RESUMO

In this paper, we present the Magnetic Resonance Image (MRI) denoising method via nonlocal multidimensional low rank tensor transformation constraint (NLRT). We first design a nonlocal MRI denoising method by non-local low rank tensor recovery framework. Furthermore, a multidimensional low rank tensor constraint is used to obtain low-rank prior information combined with 3-dimensional structure feature of MRI image cubes. Our NLRT can achieve denoising by retaining more image detail information. The optimization and updating process of the model is solved via the alternating direction method of multipliers (ADMM) algorithm. Several state-of-the-art denoising methods are selected for comparative experiments. In order to reflect the performance of the denoising method, Rician noise with different levels is added to the experiment to analyze the results. The experimental results prove that our NLTR has more outstanding denoising ability and can obtain better MRI images.

16.
J Integr Plant Biol ; 65(8): 1966-1982, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37154484

RESUMO

Higher-order chromatin organization is essential for transcriptional regulation, genome stability maintenance, and other genome functions. Increasing evidence has revealed significant differences in 3D chromatin organization between plants and animals. However, the extent, pattern, and rules of chromatin organization in plants are still unclear. In this study, we systematically identified and characterized long-range chromatin loops in the Arabidopsis 3D genome. We identified hundreds of long-range cis chromatin loops and found their anchor regions are closely associated with H3K27me3 epigenetic modifications. Furthermore, we demonstrated that these chromatin loops are dependent on Polycomb group (PcG) proteins, suggesting that the Polycomb repressive complex 2 (PRC2) complex is essential for establishing and maintaining these novel loops. Although most of these PcG-medicated chromatin loops are stable, many of these loops are tissue-specific or dynamically regulated by different treatments. Interestingly, tandemly arrayed gene clusters and metabolic gene clusters are enriched in anchor regions. Long-range H3K27me3-marked chromatin interactions are associated with the coregulation of specific gene clusters. Finally, we also identified H3K27me3-associated chromatin loops associated with gene clusters in Oryza sativa and Glycine max, indicating that these long-range chromatin loops are conserved in plants. Our results provide novel insights into genome evolution and transcriptional coregulation in plants.


Assuntos
Arabidopsis , Histonas , Animais , Histonas/metabolismo , Cromatina/genética , Cromatina/metabolismo , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Cromossomos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas/metabolismo , Família Multigênica
17.
BMC Med Educ ; 23(1): 341, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37193976

RESUMO

BACKGROUND: To investigate the use of flipped classroom pedagogy based on "Internet plus" in teaching viral hepatitis in the lemology course during the COVID-19 epidemic. METHODS: This study included students from the clinical medicine general practitioner class at Nanjing Medical University's Kangda College, with the observation group consisting of 67 students from the 2020-2021 school year and the control group consisting of 70 students from the 2019-2020 school year. The observation group used "Internet plus" flipped classroom pedagogy, while the control group used conventional offline instruction. The theory course and case analysis ability scores from the two groups were compared and analyzed, and questionnaire surveys were administered to the observation group. RESULT: After the flipped classroom, the observation group had significantly higher theoretical test scores (38.62 ± 4.52) and case analysis ability scores (21.08 ± 3.58) than the control group (37.37 ± 2.43) (t = 2.024, P = 0.045) and (19.16 ± 1.15) (t = 4.254, P < 0.001), respectively. The questionnaire survey in the observation group revealed that the "Internet plus" flipped classroom pedagogy approach can help enhance students' enthusiasm to learn, clinical thinking ability, practical application ability, and learning efficiency, with satisfaction rates of 81.7%, 85.0%, 83.3%, and 78.8%, respectively; 89.4% of students expressed hope that whenever physical classes resumed, the offline courses could be combined with this pedagogy approach. CONCLUSION: The use of the "Internet plus" flipped classroom pedagogy technique for teaching viral hepatitis in a lemology course boosted students' theory learning ability as well as their case analysis ability. The majority of students were pleased with this type of instruction and hoped that whenever physical classes resumed, the offline courses may be integrated with the "Internet plus" flipped classroom pedagogical approach.


Assuntos
COVID-19 , Estudantes de Enfermagem , Humanos , Aprendizagem Baseada em Problemas/métodos , Aprendizagem , Exame Físico , Currículo , Ensino
18.
Theranostics ; 13(8): 2588-2604, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215564

RESUMO

Background: The balance between the differentiation and self-renewal of satellite cells (SCs) is essential for skeletal muscle homeostasis and regeneration. Our knowledge of this regulatory process is incomplete. Methods: Using global and conditional knockout mice as in vivo models and isolated satellite cells as in vitro system, we investigated the regulatory mechanisms of IL34 in the process of skeletal muscle regeneration in vivo and in vitro. Results: Myocytes and regenerating fibers are major source of IL34. Deletion of interleukin 34 (IL34) sustains expansion by sacrificing the differentiation of SCs and leads to significant muscle regeneration defects. We further found that inactivating IL34 in SCs leads to hyperactivation of NFKB1 signaling; NFKB1 translocates to the nucleus and binds to the promoter region of Igfbp5 to synergistically disturb protein kinase B (Akt) activity. Notably, augmented Igfbp5 function in SCs led to deficient differentiation and Akt activity. Furthermore, disrupting Akt activity both in vivo and in vitro mimicked the phenotype of IL34 knockout. Finally, deleting IL34 or interfering Akt in mdx mice ameliorates dystrophic muscles. Conclusion: We comprehensively characterized regenerating myofibers-expressed IL34 plays a pivotal role in controlling myonuclear domain. The results also indicate that impairing IL34 function by promoting SC maintenance can lead to improved muscular performance in mdx mice in which the stem cell pool is compromised.


Assuntos
Interleucinas , Distrofia Muscular de Duchenne , Animais , Camundongos , Modelos Animais de Doenças , Distrofina/genética , Distrofina/metabolismo , Camundongos Endogâmicos mdx , Camundongos Knockout , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células-Tronco/metabolismo , Interleucinas/genética
19.
Plant J ; 115(1): 155-174, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37025008

RESUMO

Salicylic acid (SA) plays important roles in different aspects of plant development, including root growth, where auxin is also a major player by means of its asymmetric distribution. However, the mechanism underlying the effect of SA on the development of rice roots remains poorly understood. Here, we show that SA inhibits rice root growth by interfering with auxin transport associated with the OsPIN3t- and clathrin-mediated gene regulatory network (GRN). SA inhibits root growth as well as Brefeldin A-sensitive trafficking through a non-canonical SA signaling mechanism. Transcriptome analysis of rice seedlings treated with SA revealed that the OsPIN3t auxin transporter is at the center of a GRN involving the coat protein clathrin. The root growth and endocytic trafficking in both the pin3t and clathrin heavy chain mutants were SA insensitivity. SA inhibitory effect on the endocytosis of OsPIN3t was dependent on clathrin; however, the root growth and endocytic trafficking mediated by tyrphostin A23 (TyrA23) were independent of the pin3t mutant under SA treatment. These data reveal that SA affects rice root growth through the convergence of transcriptional and non-SA signaling mechanisms involving OsPIN3t-mediated auxin transport and clathrin-mediated trafficking as key components.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Oryza , Clatrina/metabolismo , Proteínas de Arabidopsis/metabolismo , Oryza/metabolismo , Arabidopsis/genética , Ácido Salicílico/metabolismo , Raízes de Plantas/metabolismo , Transporte Proteico , Ácidos Indolacéticos/metabolismo
20.
Plant Cell ; 35(7): 2484-2503, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37070946

RESUMO

Three-dimensional (3D) chromatin organization is highly dynamic during development and seems to play a crucial role in regulating gene expression. Self-interacting domains, commonly called topologically associating domains (TADs) or compartment domains (CDs), have been proposed as the basic structural units of chromatin organization. Surprisingly, although these units have been found in several plant species, they escaped detection in Arabidopsis (Arabidopsis thaliana). Here, we show that the Arabidopsis genome is partitioned into contiguous CDs with different epigenetic features, which are required to maintain appropriate intra-CD and long-range interactions. Consistent with this notion, the histone-modifying Polycomb group machinery is involved in 3D chromatin organization. Yet, while it is clear that Polycomb repressive complex 2 (PRC2)-mediated trimethylation of histone H3 on lysine 27 (H3K27me3) helps establish local and long-range chromatin interactions in plants, the implications of PRC1-mediated histone H2A monoubiquitination on lysine 121 (H2AK121ub) are unclear. We found that PRC1, together with PRC2, maintains intra-CD interactions, but it also hinders the formation of H3K4me3-enriched local chromatin loops when acting independently of PRC2. Moreover, the loss of PRC1 or PRC2 activity differentially affects long-range chromatin interactions, and these 3D changes differentially affect gene expression. Our results suggest that H2AK121ub helps prevent the formation of transposable element/H3K27me1-rich long loops and serves as a docking point for H3K27me3 incorporation.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Histonas/genética , Histonas/metabolismo , Proteínas de Arabidopsis/metabolismo , Lisina/metabolismo , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Cromatina/genética , Cromatina/metabolismo , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...