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BACKGROUND: As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. METHODS: A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-ß (TGF-ß) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). RESULTS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p < 0.0001). Immunofluorescence staining identified astrocytes with neuroblasts and immature neurons cell properties at the site of injury while neuronal marker-specific staining revealed an increased number of mature astrocytes at the injury site. Behavioral assessments showed that the intervention did not improve The BMS (Basso mouse scale) score (p = 0.0726) and gait (p > 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p < 0.0001) and a significant improvement in glial scar proliferation. Electrophysiological assessments revealed a significant improvement in spinal nerve conduction (p < 0.0001) while immunostaining revealed that the levels of TGF-ß protein at the site of injury in the intervention group were lower than control group (p = 0.0034); in addition, P70 s6 and PP2A related to the TGF-ß pathway showed ascending trend (p = 0.0036, p = 0.0152 respectively). CONCLUSIONS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord after spinal cord injury can reprogram astrocytes into neurons and significantly enhance cell regeneration at the injury site. The reprogramming of astrocytes can lead to tissue repair, thus improving the reduced threshold and increasing voluntary movements. This strategy can also improve the integrity of the blood-spinal cord barrier and enhance nerve conduction function. However, the simple reprogramming of astrocytes cannot lead to significant improvements in the striding function of the lower limbs.
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Astrocitos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Modelos Animales de Enfermedad , Proteínas del Tejido Nervioso , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Astrocitos/fisiología , Proteínas del Tejido Nervioso/metabolismo , Ratones , Regeneración Nerviosa/fisiología , Neuronas , Femenino , Ratones Endogámicos C57BL , Médula Espinal/metabolismoRESUMEN
The tribe Potentilleae comprises approximately 1700 species in 13 genera, making it one of the largest of the 16 tribes in Rosaceae. Our understanding of the composition and relationships among members of Potentilleae has advanced dramatically with the application of molecular markers in the last two decades. Yet there is still much work remaining toward a robust phylogenetic framework for the entire Potentilleae and a comprehensive genus-level dating framework for the tribe. The goals of the present study were to establish a phylogenetic framework for Potentilleae, infer the origin and diversification of the tribe using a temporal framework, and explore the taxonomic implications in light of the updated phylogenetic framework. We used the plastome sequences from 158 accessions representing 139 taxa covering all 13 recognized genera of the tribe to reconstruct the Potentilleae phylogeny. High phylogenetic resolution was recovered along the Potentilleae backbone. Two major clades were recovered within Potentilleae, corresponding to the two subtribes Fragariinae and Potentillinae. Within Fragariinae, two subclades were recovered. In one subclade, Sibbaldia sensu stricto is sister to a clade containing Sibbaldianthe, Comarum, Farinopsis, and Alchemilla sensu lato. In the other subclade, Fragaria is sister to a clade comprising Chamaerhodos, Chamaecallis, Drymocallis, Dasiphora, and Potaninia. Within Potentillinae, Argentina is sister to Potentilla sensu stricto. Within Potentilla sensu stricto, clade Himalaya is sister to Alba, and the Himalaya-Alba clade together is sister to a clade comprising Reptans, Potentilla ancistrifolia Bunge, Fragarioides, Ivesioid, and Argentea. Divergence time estimates indicated that tribe Potentilleae originated during the middle Eocene, and subtribes Fragariinae and Potentillinae diverged around the Eocene-Oligocene transition, and divergence times dated for Potentilleae genera ranged from the early Miocene to the late Pleistocene.
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Rosaceae , Filogenia , Plastidios/genética , ArgentinaRESUMEN
Janus protein tyrosine kinase (JAK) has the ability to activate signal transducer and activator of transcription (STAT). STAT3 is a valued member of the JAK/STAT signaling pathway. In recent years, several studies have documented that STAT3 is closely related to the occurrence and development of liver fibrosis caused by various factors. Activation of STAT3 can play anti- or pro-inflammatory roles in the pathogenesis of liver fibrosis. This article reviewed the recent studies on STAT3 in the development of various liver fibrosis to find a more effective method to relieve and cure liver diseases, such as hepatitis B virus (HBV), non-alcoholic fatty liver disease (NAFLD), schistosomiasis, and chemical liver injury.
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ADN/genética , Regulación de la Expresión Génica , Cirrosis Hepática/genética , Factor de Transcripción STAT3/genética , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/metabolismo , Factor de Transcripción STAT3/biosíntesis , Transducción de SeñalRESUMEN
Functional neck motion is achieved by the cervical segments with each composed of an intervertebral disc (IVD) and two facet joints (FJs). Using biplane fluoroscopic imaging, we investigated the ranges of motion (ROMs) of the three joints in the cervical spines (from C3 to C7) of eighteen asymptomatic subjects. Three functional neck motions were examined, including flexion-extension (FE), lateral bending (LB) and axial twisting (AT). Our measurements showed that the translations of both IVD and FJs primarily occurred in the sagittal plane during all neck motions, and the anteroposterior translations of IVDs were significantly smaller than those of the corresponding FJs (p < 0.05) at all segments. For example, the ranges of IVD and FJ anteroposterior translations at C3/4 were 2.7 ± 0.7 mm vs. 3.5 ± 1.1 mm in FE, 0.9 ± 0.5 mm vs. 4.6 ± 1.1 mm in LB, and 1.0 ± 0.5 mm vs. 3.1 ± 1.0 mm in AT. Furthermore, we introduced an IVD-FJ translation ratio, which represents the ratio of the IVD to FJ translational ROMs. In FE neck motion, the IVD-FJ anteroposterior translation ratios decreased from 0.81 ± 0.18 at C3 to 0.52 ± 0.19 at C3, indicating gradually increasing resistances of IVDs compared to FJs from the proximal to distal levels. In LB neck motion, the smallest IVD-FJ translation ratios (0.14 ± 0.09 and 0.43 ± 0.30) occurred at C4/5 for both anteroposterior and left-right translations. In AT neck motion, the largest IVD-FJ anteroposterior translation ratio (0.42 ± 0.21) occurred at C3/4, and was significantly different from those at C4/5 and C5/6 (p < 0.05). These data could be used as references for improving motion-preserving cervical treatment methods that aimed to achieve the normal ranges of translational motions of both IVD and FJs.
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Disco Intervertebral , Articulación Cigapofisaria , Fenómenos Biomecánicos , Vértebras Cervicales/diagnóstico por imagen , Humanos , Rango del Movimiento Articular , Articulación Cigapofisaria/diagnóstico por imagenRESUMEN
The Fig. 1b is wrongly published in the original publication of the article. The correct version of Fig. 1b is presented in this Correction.
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In this work, a novel CdS-SnS-SnS2/rGO photocatalyst with two tin valence states (â ¡ and IV) was successfully synthesized by a one-pot solvothermal method. For comparison, CdS-SnS2/rGO (GCS2) with tin in only the IV valence state was made by the same method. Based on a series of characterizations, CdS, SnS and SnS2 were shown to be successfully loaded onto the rGO surface. The introduction of rGO may increase charge carrier separation. The degradation efficiency increased gradually with increasing rGO loading content, and the optimum photocatalytic activity was observed at 6.0 wt% rGO loading content (GCS1), which achieved the efficient removal (84.46%) of ibuprofen over 60 min. Compared with GCS2, the CdS-SnS-SnS2/rGO composite exhibited significantly improved photocatalytic performance, which can be ascribed to the formation of a double heterostructure. rGO worked as a transfer mediator to transfer electrons from the conduction band (CB) of SnS to the CB of SnS2 at the heterointerface, which then flowed to the CB of CdS because of another heterojunction, further enhancing the separation efficiency of photogenerated carriers. Therefore, this study highlights a novel double heterojunction system with a facial preparation method, visible light response and good recyclability, which is beneficial for environmental remediation.
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BACKGROUND: Hematoporphyrin derivative (HPD) has a sensibilization effect in lung adenocarcinoma. This study was conducted to identify the target genes of HPD in lung adenocarcinoma. METHODS: RNA sequencing was performed using the lung adenocarcinoma cell line A549 after no treatment or treatment with X-ray or X-ray + HPD. The differentially expressed genes (DEGs) were screened using Mfuzz package by noise-robust soft clustering analysis. Enrichment analysis was carried out using "BioCloud" online tool. Protein-protein interaction (PPI) network and module analyses were performed using Cytoscape software. Using WebGestalt tool and integrated transcription factor platform (ITFP), microRNA target and transcription factor (TF) target pairs were separately predicted. An integrated regulatory network was visualized with Cytoscape software. RESULTS: A total of 815 DEGs in the gene set G1 (continuously dysregulated genes along with changes in processing conditions [untreated-treated with X-ray-X-ray + treated with HPD]) and 464 DEGs in the gene set G2 (significantly dysregulated between X-ray + HPD-treated group and untreated/X-ray-treated group) were screened. The significant module identified from the PPI network for gene set G1 showed that ribosomal protein L3 (RPL3) gene could interact with heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1). TFs AAA domain containing 2 (ATAD2) and protein inhibitor of activated STAT 1 (PIAS1) were separately predicted for the genes in gene set G1 and G2, respectively. In the integrated network for gene set G2, ubiquitin-specific peptidase 25 (USP25) was targeted by miR-200b, miR-200c, and miR-429. CONCLUSION: RPL3, HSP90AA1, ATAD2, and PIAS1 as well as USP25, which is targeted by miR-200b, miR-200c, and miR-429, may be the potential targets of HPD in lung adenocarcinoma.
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Adenocarcinoma del Pulmón/genética , Redes Reguladoras de Genes/genética , Derivado de la Hematoporfirina/farmacología , Neoplasias Pulmonares/genética , ATPasas Asociadas con Actividades Celulares Diversas/efectos de los fármacos , ATPasas Asociadas con Actividades Celulares Diversas/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/radioterapia , Línea Celular Tumoral , Análisis por Conglomerados , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/genética , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Proteínas HSP90 de Choque Térmico/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , MicroARNs/metabolismo , Proteínas Inhibidoras de STAT Activados/efectos de los fármacos , Proteínas Inhibidoras de STAT Activados/genética , Proteína Ribosomal L3 , Proteínas Ribosómicas/efectos de los fármacos , Proteínas Ribosómicas/genética , Análisis de Secuencia de ARN , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/efectos de los fármacos , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética , Factores de TranscripciónRESUMEN
BACKGROUND: Hematoporphyrin derivative (HPD) has a sensibilization effect in lung adenocarcinoma. This study was conducted to identify the target genes of HPD in lung adenocarcinoma. METHODS: RNA sequencing was performed using the lung adenocarcinoma cell line A549 after no treatment or treatment with X-ray or X-ray + HPD. The differentially expressed genes (DEGs) were screened using Mfuzz package by noise-robust soft clustering analysis. Enrichment analysis was carried out using "BioCloud" online tool. Protein-protein interaction (PPI) network and module analyses were performed using Cytoscape software. Using WebGestalt tool and integrated transcription factor platform (ITFP), microRNA target and transcription factor (TF) target pairs were separately predicted. An integrated regulatory network was visualized with Cytoscape software. RESULTS: A total of 815 DEGs in the gene set G1 (continuously dysregulated genes along with changes in processing conditions [untreated-treated with X-ray-X-ray + treated with HPD]) and 464 DEGs in the gene set G2 (significantly dysregulated between X-ray + HPD-treated group and untreated/X-ray-treated group) were screened. The significant module identified from the PPI network for gene set G1 showed that ribosomal protein L3 (RPL3) gene could interact with heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1). TFs AAA domain containing 2 (ATAD2) and protein inhibitor of activated STAT 1 (PIAS1) were separately predicted for the genes in gene set G1 and G2, respectively. In the integrated network for gene set G2, ubiquitin-specific peptidase 25 (USP25) was targeted by miR-200b, miR-200c, and miR-429. CONCLUSION: RPL3, HSP90AA1, ATAD2, and PIAS1 as well as USP25, which is targeted by miR-200b, miR-200c, and miR-429, may be the potential targets of HPD in lung adenocarcinoma.
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Humanos , Derivado de la Hematoporfirina/farmacología , Redes Reguladoras de Genes/genética , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Proteínas Ribosómicas/efectos de los fármacos , Proteínas Ribosómicas/genética , Factores de Transcripción , Análisis por Conglomerados , Regulación Neoplásica de la Expresión Génica , Análisis de Secuencia de ARN , Proteínas HSP90 de Choque Térmico/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/genética , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/efectos de los fármacos , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/genética , Proteínas Inhibidoras de STAT Activados/efectos de los fármacos , Proteínas Inhibidoras de STAT Activados/genética , Citometría de Flujo , ATPasas Asociadas con Actividades Celulares Diversas/efectos de los fármacos , ATPasas Asociadas con Actividades Celulares Diversas/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapiaRESUMEN
In this work, we report the cloning and characterization of endo-ß-1,4-glucanase (EGase) genes (TaEG) in the common wheat line three pistils. Three TaEG homoeologous genes (TaEG-4A, TaEG-4B and TaEG-4D) were isolated and found to be located on chromosomes 4AL, 4BS and 4DS, respectively. The three genes showed high conservation of their coding nucleotide sequences and 3 untranslated region. The putative TaEG protein had a molecular mass of 69 kDa, a theoretical pI of 9.39 and a transmembrane domain of 74-96 amino acids in the N-terminus that anchored the protein to the membrane. The genome sequences of TaEG-4A, TaEG-4B and TaEG-4D contained six exons and five introns. All of the introns, except for intron IV, varied in length and sequence composition. Phylogenetic analysis revealed that TaEG was most closely related to rice (Oryza sativa) OsGLU1. The TaEG transcript levels increased significantly during the subsidiary pistil primordium differentiation phase (spike size â¼7-10 mm) in Chuanmai 28 TP (CM28TP). These data provide a basis for future research into the function of TaEG and offer insights into the molecular mechanism of the three pistils mutation in wheat.
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PURPOSE: To study the impact of seed localization, as performed by different observers using linked (125)I seeds, on postimplant dosimetry in prostate brachytherapy and, to compare transrectal ultrasound (TRUS)-based with CT-based approach for the dosimetric outcomes. METHODS AND MATERIALS: Nineteen permanent prostate implants were conducted using linked (125)I seeds. Postimplant TRUS and CT images were acquired and prostate glands were, after implantation, delineated on all images by a single oncologist, who had performed all 19 seeding procedures. Six observers independently localized the seeds on both TRUS and CT images, from which the principle dosimetric parameters V(100) (volume of prostate that received the prescribed dose), V(150) (volume of prostate that received 150% of the prescribed dose), and D(90) (minimal dose delivered to 90% of the prostate) were directly calculated for each patient. A single-factor analysis of variance was first applied to determine interobserver variability in seed localization. A nonparametric comparison of the approach using TRUS and CT was then carried out by the Wilcoxon paired-sample test. RESULTS: Analysis from the analysis of variance for TRUS showed that the null hypothesis for equal means, could not be rejected for all six observers based on a significance level alpha=0.05. TRUS-based and CT-based approaches were then cross compared by the Wilcoxon paired-sample test, which suggested that the null hypothesis was insignificant for V(100) and D(90), but was significant for V(150). CONCLUSIONS: Both TRUS- and CT-imaging modalities provided indistinguishable postimplant dosimetry results as far as V(100) and D(90) were concerned. There was comparable observer independence between TRUS- and CT-based seed localization for linked-seed implant procedures. With other advantages that TRUS-imaging modality had over CT in the evaluation of postimplant dosimetry, TRUS would be a preferred choice in conjunction with linked seeds for intraoperative procedures in prostate brachytherapy.