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1.
FASEB J ; 38(7): e23534, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38597911

RESUMEN

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.


Asunto(s)
Sistema de Señalización de MAP Quinasas , Osteonectina , Animales , Ratones , División Celular Asimétrica , Diferenciación Celular , Osteonectina/genética , Transducción de Señal
2.
Artículo en Inglés | MEDLINE | ID: mdl-38657655

RESUMEN

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.

3.
Biomed Pharmacother ; 174: 116448, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38522241

RESUMEN

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.


Asunto(s)
Microbioma Gastrointestinal , Levodopa , Enfermedad de Parkinson , Ratas Sprague-Dawley , Levodopa/farmacología , Animales , Masculino , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Ratas , Microbioma Gastrointestinal/efectos de los fármacos , Antiparkinsonianos/farmacología , Rotenona/farmacología , Nardostachys/química , Dopamina/metabolismo , Conducta Animal/efectos de los fármacos
4.
Artículo en Inglés | MEDLINE | ID: mdl-38556538

RESUMEN

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.

5.
Cell Prolif ; : e13612, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38348888

RESUMEN

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.

6.
Plant Cell ; 36(4): 1098-1118, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38092516

RESUMEN

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.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , alfa-Cristalinas , Arabidopsis/genética , Arabidopsis/metabolismo , Genes de ARNr , Metilación de ADN/genética , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , ADN Ribosómico/genética , ADN Ribosómico/metabolismo , alfa-Cristalinas/genética , alfa-Cristalinas/metabolismo
7.
Comput Methods Biomech Biomed Engin ; 27(3): 296-305, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36939836

RESUMEN

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.


Asunto(s)
Aparatos Ortodóncicos Removibles , Tracción , Análisis de Elementos Finitos , Diente Molar/cirugía , Ligamento Periodontal , Maxilar/cirugía , Técnicas de Movimiento Dental
8.
Adv Sci (Weinh) ; 10(36): e2303545, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37963851

RESUMEN

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.


Asunto(s)
Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/metabolismo , Polaridad Celular , Centrosoma/metabolismo , Fenotipo
9.
BMC Public Health ; 23(1): 2228, 2023 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-37953277

RESUMEN

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.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Análisis de Costo-Efectividad , Didesoxinucleósidos/efectos adversos , Lamivudine/efectos adversos , Antirretrovirales/uso terapéutico , Emtricitabina/uso terapéutico , Benzoxazinas/uso terapéutico
10.
Molecules ; 28(12)2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37375355

RESUMEN

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.


Asunto(s)
Bacterias , Ácidos Grasos Volátiles , Animales , Abejas , Fermentación , Ácidos Grasos Volátiles/análisis , Fenoles/química , Polen/química , Bacteroidetes , Fibras de la Dieta/análisis
11.
Int. j. morphol ; 41(3): 889-893, jun. 2023. ilus, tab
Artículo en Inglés | LILACS | ID: biblio-1514319

RESUMEN

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.


Asunto(s)
Humanos , Niño , Postura , Vértebras Cervicales/anatomía & histología , Cabeza/anatomía & histología , Maloclusión de Angle Clase III/terapia , Cefalometría , Puntos Anatómicos de Referencia
12.
J Integr Plant Biol ; 65(8): 1966-1982, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37154484

RESUMEN

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.


Asunto(s)
Arabidopsis , Histonas , Animales , Histonas/metabolismo , Cromatina/genética , Cromatina/metabolismo , Proteínas del Grupo Polycomb/genética , Proteínas del Grupo Polycomb/metabolismo , Cromosomas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas/metabolismo , Familia de Multigenes
13.
Artículo en Inglés | MEDLINE | ID: mdl-37159088

RESUMEN

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.

14.
BMC Med Educ ; 23(1): 341, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37193976

RESUMEN

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.


Asunto(s)
COVID-19 , Estudiantes de Enfermería , Humanos , Aprendizaje Basado en Problemas/métodos , Aprendizaje , Examen Físico , Curriculum , Enseñanza
15.
Artículo en Inglés | MEDLINE | ID: mdl-37141056

RESUMEN

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.
Theranostics ; 13(8): 2588-2604, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215564

RESUMEN

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.


Asunto(s)
Interleucinas , Distrofia Muscular de Duchenne , Animales , Ratones , Modelos Animales de Enfermedad , Distrofina/genética , Distrofina/metabolismo , Ratones Endogámicos mdx , Ratones Noqueados , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células Madre/metabolismo , Interleucinas/genética
17.
Plant Cell ; 35(7): 2484-2503, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37070946

RESUMEN

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.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Histonas/genética , Histonas/metabolismo , Proteínas de Arabidopsis/metabolismo , Lisina/metabolismo , Proteínas del Grupo Polycomb/genética , Proteínas del Grupo Polycomb/metabolismo , Cromatina/genética , Cromatina/metabolismo , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismo
18.
Plant J ; 115(1): 155-174, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37025008

RESUMEN

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.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Oryza , Clatrina/metabolismo , Proteínas de Arabidopsis/metabolismo , Oryza/metabolismo , Arabidopsis/genética , Ácido Salicílico/metabolismo , Raíces de Plantas/metabolismo , Transporte de Proteínas , Ácidos Indolacéticos/metabolismo
19.
Int J STD AIDS ; 34(7): 468-475, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36935424

RESUMEN

OBJECTIVE: To estimate 30-day hospital readmission rates among persons living with HIV (PLWH) at the Nantong Infectious Disease Hospital in China and analyse the related risk factors. METHODS: A single-centre retrospective cohort study was conducted. There were 894 PLWH records obtained from the electronic medical record (EMR) system at the Nantong Infectious Disease Hospital in China, from October 2013 to February 2018. The 30-day readmission rates were calculated, and the risk factors were analysed by generalised estimating equations (GEEs). RESULTS: A total of 1153 hospitalizations from 894 patients were recorded between October 2013 and February 2018. The median time of 30-day readmissions was 13 days (interquartile range (IQR), 6-23). The reasons for all causes, acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs), and non-AIDS-defining infections (non-ADIs) were 9.08, 13.52, and 7.91%, respectively. The results from the GEE analysis demonstrated that the risk factors associated with 30-days readmissions were as follows: no antiretroviral therapy (ART) prior to hospitalisations (odds ratio (OR) = 1.90, 95% confidence interval (CI): 1.21-3.00), low CD4 counts (OR = 2.17, 95% CI: 1.33-3.54), and multiple comorbidities (OR = 6.45, 95% CI: 1.62-25.73). CONCLUSION: Early detection of HIV infection and early initiation of ART treatment are the keys to controlling 30-day readmissions.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Readmisión del Paciente , Estudios Retrospectivos , Factores de Riesgo , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Hospitales , China/epidemiología
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(2): 165-171, 2023 Feb 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-36999462

RESUMEN

OBJECTIVES: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC. METHODS: We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients. RESULTS: The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r=0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P=0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low. CONCLUSIONS: Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteínas Proto-Oncogénicas c-myc/metabolismo , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/diagnóstico , Carcinoma de Células Escamosas/genética , Metástasis Linfática , Pronóstico , Biomarcadores de Tumor/metabolismo , Proteínas de Unión al ARN/genética
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