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1.
Plant Physiol ; 191(3): 1871-1883, 2023 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-36464768

RESUMEN

Changes in plant auxin levels can be perceived and converted into cellular responses by auxin signal transduction. AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) proteins are auxin transcriptional inhibitors that play important roles in regulating auxin signal transduction. The stability of Aux/IAA proteins is important for transcription initiation and downstream auxin-related gene expression. Here, we report that the Aux/IAA protein IAA17 interacts with the small ubiquitin-related modifier (SUMO) E3 ligase METHYL METHANESULFONATE-SENSITIVE 21 (AtMMS21) in Arabidopsis (Arabidopsis thaliana). AtMMS21 regulated the SUMOylation of IAA17 at the K41 site. Notably, root length was suppressed in plants overexpressing IAA17, whereas the roots of K41-mutated IAA17 transgenic plants were not significantly different from wild-type roots. Biochemical data indicated that K41-mutated IAA17 or IAA17 in the AtMMS21 knockout mutant was more likely to be degraded compared with nonmutated IAA17 in wild-type plants. In conclusion, our data revealed a role for SUMOylation in the maintenance of IAA17 protein stability, which contributes to improving our understanding of the mechanisms of auxin signaling.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Transducción de Señal , Sumoilación , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
2.
Clin Exp Rheumatol ; 42(9): 1736-1743, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38530663

RESUMEN

OBJECTIVES: To explore the effectiveness of tofacitinib for immunoglobulin G4-related disease (IgG4-RD) and idiopathic retroperitoneal fibrosis (IRF), and investigate the expression of JAKs in the lesion of these diseases. METHODS: Clinical data of patients with IgG4-RD or IRF who were administered with tofacitinib monotherapy were collected. IgG4-RD responder index (IgG4-RD RI) was assessed. The expression of JAK1, JAK2, JAK3, and TYK2 were analysed with immunohistochemistry staining in three salivary glands specimens of IgG4-RD and one retroperitoneal tissue of IRF. RESULTS: Two patients with IRF and two patients with IgG4-RD used tofacitinib monotherapy. Two patients with IRF achieved complete remission with diminished retroperitoneal mass and decreased CRP, as IgG4-RD RI decreased from 6 to 1 in both of them. One with IgG4-RD achieved complete remission with alleviated enlargement of pancreas and IgG4 level decreased from 13.7 g/L to 2.4 g/L, as IgG4-RD RI decreased from 12 to 1. One with IgG4-RD achieved partial response with IgG4 level decreased from 77.1g/L to 25.8g/L as IgG4-RD RI from 18 to 6. JAK1, JAK2, JAK3, and TYK2 expression were detected in biopsy tissues. The staining intensity of the JAK family on the lesion from one IRF patient was similar to those from IgG4-RD patients. CONCLUSIONS: Tofacitinib is a potentially effective treatment for IgG4-RD and IRF and it is reasonable to conduct clinical trial to validate its efficacy. The JAKs were expressed in the inflammatory lesions of IgG4-RD and IRF and they may share a common pathogenesis pathway that is independent of IgG4 production.


Asunto(s)
Enfermedad Relacionada con Inmunoglobulina G4 , Piperidinas , Inhibidores de Proteínas Quinasas , Pirimidinas , Fibrosis Retroperitoneal , TYK2 Quinasa , Humanos , Piperidinas/uso terapéutico , Fibrosis Retroperitoneal/tratamiento farmacológico , Pirimidinas/uso terapéutico , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del Tratamiento , Femenino , Janus Quinasa 1 , Janus Quinasa 2 , Janus Quinasa 3 , Anciano , Inducción de Remisión , Adulto , Inmunoglobulina G , Inhibidores de las Cinasas Janus/uso terapéutico
3.
Biomacromolecules ; 24(2): 667-677, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36599673

RESUMEN

Small interfering RNA (siRNA) holds promise for treating rheumatoid arthritis by inhibiting major cytokines such as tumor necrosis factor-α (TNF-α). We developed original cationic amphiphilic phosphorus dendrons to produce dendriplexes associated with TNF-α siRNA. The dendrons were made of 10 pyrrolidinium end groups and a C17 aliphatic chain. The dendriplexes demonstrated the ability to protect siRNA from nuclease degradation and to promote macrophage uptake. Moreover, they led to potent inhibition of TNF-α expression in the lipopolysaccharide-activated mouse macrophage cell line RAW264.7 in vitro model. A significant anti-inflammatory effect in the murine collagen-induced arthritis model was observed through arthritis scoring and histological observations. These results open up essential perspectives in using this original amphiphilic dendron to reduce the disease burden and improve outcomes in chronic inflammatory diseases.


Asunto(s)
Artritis Experimental , Dendrímeros , Animales , Ratones , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Factor de Necrosis Tumoral alfa/genética , Antiinflamatorios/farmacología
4.
Plant Cell ; 31(10): 2332-2352, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31427469

RESUMEN

A crucial step for mRNA polyadenylation is poly(A) signal recognition by trans-acting factors. The mammalian cleavage and polyadenylation specificity factor (CPSF) complex components CPSF30 and WD repeat-containing protein33 (WDR33) recognize the canonical AAUAAA for polyadenylation. In Arabidopsis (Arabidopsis thaliana), the flowering time regulator FY is the homolog of WDR33. However, its role in mRNA polyadenylation is poorly understood. Using poly(A) tag sequencing, we found that >50% of alternative polyadenylation (APA) events are altered in fy single mutants or double mutants with oxt6 (a null mutant of AtCPSF30), but mutation of the FY WD40-repeat has a stronger effect than deletion of the plant-unique Pro-Pro-Leu-Pro-Pro (PPLPP) domain. fy mutations disrupt AAUAAA or AAUAAA-like poly(A) signal recognition. Notably, A-rich signal usage is suppressed in the WD40-repeat mutation but promoted in PPLPP-domain deficiency. However, fy mutations do not aggravate the altered signal usage in oxt6 Furthermore, the WD40-repeat mutation shows a preference for 3' untranslated region shortening, but the PPLPP-domain deficiency shows a preference for lengthening. Interestingly, the WD40-repeat mutant exhibits shortened primary roots and late flowering with alteration of APA of related genes. Importantly, the long transcripts of two APA genes affected in fy are related to abiotic stress responses. These results reveal a conserved and specific role of FY in mRNA polyadenylation.


Asunto(s)
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Poliadenilación/genética , Señales de Poliadenilación de ARN 3'/genética , ARN Mensajero/genética , Transcriptoma/genética , Factores de Escisión y Poliadenilación de ARNm/genética , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Regiones no Traducidas 3'/genética , Factor de Especificidad de Desdoblamiento y Poliadenilación/genética , Flores/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Ontología de Genes , Redes Reguladoras de Genes , Mutación , Fenotipo , Raíces de Plantas/metabolismo , Unión Proteica , Dominios Proteicos/genética , Repeticiones WD40/genética
5.
RNA Biol ; 18(12): 2594-2604, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34036876

RESUMEN

Alternative polyadenylation (APA) is a widespread post-transcriptional modification method that changes the 3' ends of transcripts by altering poly(A) site usage. However, the longitudinal transcriptomic 3' end profile and its mechanism of action are poorly understood. We applied diurnal time-course poly(A) tag sequencing (PAT-seq) for Arabidopsis and identified 3284 genes that generated both rhythmic and arrhythmic transcripts. These two classes of transcripts appear to exhibit dramatic differences in expression and translation activisty. The asynchronized transcripts derived by APA are embedded with different poly(A) signals, especially for rhythmic transcripts, which contain higher AAUAAA and UGUA signal proportions. The Pol II occupancy maximum is reached upstream of rhythmic poly(A) sites, while it is present directly at arrhythmic poly(A) sites. Integrating H3K9ac and H3K4me3 time-course data analyses revealed that transcriptional activation of histone markers may be involved in the differentiation of rhythmic and arrhythmic APA transcripts. These results implicate an interplay between histone modification and RNA 3'-end processing, shedding light on the mechanism of transcription rhythm and alternative polyadenylation.


Asunto(s)
Arabidopsis/genética , Poliadenilación , Procesamiento Postranscripcional del ARN , ARN Mensajero/genética , ARN de Planta/genética , Transcripción Genética , Transcriptoma
6.
Physiol Plant ; 156(3): 311-22, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26294083

RESUMEN

Vitamin K epoxide reductase (VKOR) exists widely in the chloroplasts of higher plants and plays important roles in redox regulation. However, investigations of plant VKOR function have primarily focused on VKOR from Arabidopsis, and knowledge concerning this function is therefore quite limited. In this study, Solanum lycopersicum was used to study the function of VKOR. Transcription level analysis revealed that SlVKOR (S. lycopersicum VKOR) expression was upregulated by salt or drought stress. To further investigate the function of SlVKOR in plants, we generated sense and antisense transgenic S. lycopersicum homozygotes at T2 generation plants. Compared with wild-type (WT) plants, the leaf disks of the SlVKOR overexpression plants retained a much higher percentage of chlorophyll after salt or drought treatment, whereas the antisense transgenic plants displayed an opposite response. The overexpressed plants displayed lower levels of H2O2 and superoxide anion radical (O2(·-)) than WT plants, whereas antisense plants accumulated considerably more H2O2 and O2(·-). The activities of reactive oxygen scavenger enzymes, including superoxide dismutase, peroxidase, ascorbate peroxidase and catalase, were consistent with the accumulation of reactive oxygen species. Based on these results, we suggest that SlVKOR is involved in resistance to salt or drought stress.


Asunto(s)
Presión Osmótica , Homología de Secuencia de Aminoácido , Solanum lycopersicum/enzimología , Estrés Fisiológico , Vitamina K Epóxido Reductasas/metabolismo , Adaptación Fisiológica , Antioxidantes/metabolismo , Sequías , Escherichia coli/metabolismo , Regulación de la Expresión Génica de las Plantas , Peróxido de Hidrógeno/metabolismo , Solanum lycopersicum/genética , Viabilidad Microbiana , Plantas Modificadas Genéticamente , ARN sin Sentido/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Superóxidos/metabolismo
7.
Physiol Plant ; 154(1): 28-38, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25171375

RESUMEN

Arabidopsis lumen thiol oxidoreductase 1 (LTO1) - the At4g35760 gene product - was previously found to be related to reactive oxygen species (ROS) accumulation. Here, we show that ROS accumulated in a mutant Arabidopsis line (lto1-2, mutant of LTO1/AtVKOR) under osmotic stress at a higher level than that observed in wild-type and transgenic complemented plants of the lto1-2 mutant (lto1-2C, transgenic complemented plants of lto1-2). Because ROS accumulation in osmotic stress is triggered by abscisic acid (ABA), an ABA-responsive gene, Annexin 1 (AnnAt1), was selected to study the response. Osmotic stress or exogenous ABA can significantly upregulate the transcription of AnnAt1 in wild-type and lto1-2C plants. Only a slight change in the transcriptional abundance of AnnAt1 was observed under osmotic stress in the lto1-2 mutant, but exogenous ABA application could increase the expression of AnnAt1, which suggested that exogenous ABA had a partial complementation role. Because the transcription of AnnAt1 is regulated by ABRE (ABA-responsive elements) binding proteins (AREBs)/ABRE binding factors (ABFs), the expression of AREBs/ABFs was also analyzed. The transcription of AREBs/ABFs in the lto1-2 mutant was not induced by osmotic stress but was significantly upregulated by exogenous ABA, which significantly differs from the wild-type and lto1-2C plant responses. Similarly, the expression of another ABA-responsive gene, RD29B (responsive to desiccation stress gene 29B), in the lto1-2 mutant was also upregulated by exogenous ABA. The partial complementation of mutants by ABA indicated that the ABA signal transduction pathway was not significantly affected in the lto1-2 mutant. Taken together, these results suggest that LTO1 is involved in ABA-mediated response to osmotic stress, possibly by affecting the biosynthesis of endogenous ABA.


Asunto(s)
Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Presión Osmótica , Tilacoides/metabolismo , Vitamina K Epóxido Reductasas/metabolismo , Anexinas/metabolismo , Arabidopsis/genética , Proteínas y Péptidos de Choque por Frío/metabolismo , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno/metabolismo , Elementos Reguladores de la Transcripción , Vitamina K Epóxido Reductasas/genética
8.
Biochem Biophys Res Commun ; 445(2): 394-7, 2014 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-24525118

RESUMEN

Tubby-like proteins (TLPs) are found in a broad range of multicellular organisms. In mammals, genetic mutation of tubby or other TLPs can result in certain disease phenotypes related to animal specific characters: obesity, retinal degeneration, hearing loss, et al. Plants also harbor a large number of TLP genes, but the information in plants is far more limited. We identified a highly up-regulated obesity-like gene, MdTLP7, in our previous study of apple differential gene expression profile under chilling, indicating its possible role in plant abiotic stress tolerance. cDNA of MdTLP7 was amplified and expressed in Escherichia coli. In the solid and solution medium, the rate of growth and the quantity of the cell carrying MdTLP7 gene were significantly more than that of empty vector under salt and temperature stresses. To identify the functional region, serial deletion from both N-terminus and C-terminus of MdTLP7 was performed. In 415 amino acid polypeptide chain of MdTLP7, a middle conservative fragment (120-310 amino acid residues) played vital roles in stress tolerance. This fragment was involved in ß barrel of Tubby domain according to the model of Tubby domain. All above results suggested MdTLP7 confers stress-tolerance to E. coli cell against abiotic stresses.


Asunto(s)
Escherichia coli/crecimiento & desarrollo , Escherichia coli/genética , Malus/genética , Proteínas de Plantas/genética , Adaptación Fisiológica , Secuencia de Aminoácidos , Escherichia coli/fisiología , Expresión Génica , Genes de Plantas , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas de Plantas/química , Estructura Terciaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Alineación de Secuencia , Estrés Fisiológico
9.
Biochemistry (Mosc) ; 79(5): 440-9, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24954595

RESUMEN

Homologs of vitamin K epoxide reductase (VKOR) exist widely in plants. However, only VKOR of Arabidopsis thaliana has been the subject of many studies to date. In the present study, the coding region of a VKOR from Solanum lycopersicum (JF951971 in GenBank) was cloned; it contained a membrane domain (VKOR domain) and an additional soluble thioredoxin-like (Trx-like) domain. Bioinformatic analysis showed that the first 47 amino acids in the N-terminus should act as a transit peptide targeting the protein to the chloroplast. Western blot demonstrated that the protein is localized in thylakoid membrane with the Trx-like domain facing the lumen. Modeling of three-dimensional structure showed that SlVKOR has a similar conformation with Arabidopsis and cyanobacterial VKORs, with five transmembrane segments in the VKOR domain and a typical Trx-like domain in the lumen. Functional assay showed that the full-length of SlVKOR with Trx-like domain without the transit peptide could catalyze the formation of disulfide bonds. Similar transit peptides at the N-terminus commonly exist in plant VKORs, most of them targeting to chloroplast according to prediction. Comparison of sequences and structures from different plants indicated that all plant VKORs possess two domains, a transmembrane VKOR domain and a soluble Trx-like domain, each having four conservative cysteines. The cysteines were predicted to be related to the function of catalyzing the formation of disulfide bonds.


Asunto(s)
Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Vitamina K Epóxido Reductasas/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Cloroplastos/metabolismo , Clonación Molecular , Biología Computacional , Datos de Secuencia Molecular , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/clasificación , Estructura Terciaria de Proteína , Vitamina K Epóxido Reductasas/química , Vitamina K Epóxido Reductasas/clasificación
10.
Clin Rheumatol ; 43(6): 1855-1863, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38704780

RESUMEN

INTRODUCTION: Rheumatoid arthritis (RA) often leads to interstitial lung disease (ILD), significantly affecting patient outcomes. This study explored the diagnostic accuracy of a multi-biomarker approach to offer a more efficient and accessible diagnostic strategy for RA-associated ILD (RA-ILD). METHODS: Patients diagnosed with RA, with or without ILD, at Beijing Tiantan Hospital from October 2019 to October 2023 were analyzed. A total of 125 RA patients were included, with 76 diagnosed with RA-ILD. The study focused on three categories of indicators: tumor markers, inflammatory indicators, and disease activity measures. The heatmap correlation analysis was employed to analyze the correlation among these indicators. Logistic regression was used to determine odds ratios (OR) for indicators linked to RA-ILD risk. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of these indicators for RA-ILD. RESULTS: The results of logistic regression analysis showed that tumor markers (carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1)), as well as inflammatory indicators (neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet, C-reactive protein (CRP)) and disease activity measures (disease activity score-28-CRP (DAS28-CRP), rheumatoid factor (RF), and anti-cyclic peptide containing citrulline (anti-CCP)), were significantly associated with RA-ILD. The correlation coefficients among these indicators were relatively low. Notably, the combination indicator 4, which integrated the aforementioned three categories of biomarkers, demonstrated improved diagnostic accuracy with an AUC of 0.857. CONCLUSION: The study demonstrated that combining tumor markers, inflammatory indicators, and disease activity measures significantly enhanced the prediction of RA-ILD. Key Points • Multidimensional strategy: Integrated tumor markers, inflammatory indicators, and disease activity measures to enhance early detection of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). • Diagnostic accuracy: Employed heatmap correlation and logistic regression, identifying significant associations and improving diagnostic accuracy with a multidimensional biomarker combination. • Superior performance: The combined multidimensional biomarker strategy demonstrated higher diagnostic precision compared to individual or dual-category indicators. • Clinical relevance: Offers a promising, accessible approach for early detection of RA-ILD in clinical settings, potentially improving patient outcomes.


Asunto(s)
Artritis Reumatoide , Biomarcadores de Tumor , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/etiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Anciano , Biomarcadores/sangre , Curva ROC , Modelos Logísticos , Queratina-19/sangre , Adulto , Proteína C-Reactiva/análisis , Índice de Severidad de la Enfermedad , Antígeno CA-19-9/sangre , Antígenos de Neoplasias
11.
Sci Rep ; 14(1): 5783, 2024 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461210

RESUMEN

To investigate the clinical characteristics of Guillain-Barré syndrome (GBS) in patients with primary Sjögren's syndrome (SS). Records of patients with positive anti-SSA antibodies hospitalized in the Beijing Tiantan Hospital between December 2011 and May 2020 were retrieved. Patients who fulfilled the criteria for diagnosis of GBS and primary SS were included, and their clinical data were analyzed. Among the 785 patients with positive anti-SSA, 52 patients were identified in this study. They were 27 males and 25 females with median age of 59 years old. Besides anti-SSA antibodies, multiple autoantibodies were detected in these patients including antinuclear antibody, anti-Ro52, anti-mitochondrial M2, anti-thyroid peroxidase and anti-thyroglobulin autoantibodies. Preceding infection was reported in 42 patients. Hyporeflexia/areflexia and limbs weakness were the most common manifestation and 35 patients presented cranial nerve injuries. GBS disability score of 3, 4 and 5 was scaled in 28 (53.8%), 15 (28.8%) and 3 (5.8%) patients respectively. Forty-six patients received intravenous immunoglobulin (IVIG) monotherapy, 5 patients were treated by IVIG plus glucocorticoids, and 51 patients improved during hospitalization. The frequency of male gender among the patients with both GBS and primary SS suggests an independent onset of GBS and the co-existence of these autoimmune diseases in patients with multiple autoantibodies. Majority of patients with GBS and primary SS experience benign disease course.


Asunto(s)
Enfermedades Autoinmunes , Síndrome de Guillain-Barré , Síndrome de Sjögren , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Guillain-Barré/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome de Sjögren/diagnóstico , Autoanticuerpos , Enfermedades Autoinmunes/tratamiento farmacológico
12.
Mol Plant ; 17(9): 1392-1406, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39066483

RESUMEN

Under warm temperatures, plants adjust their morphologies for environmental adaption via precise gene expression regulation. However, the function and regulation of alternative polyadenylation (APA), an important fine-tuning of gene expression, remains unknown in plant thermomorphogenesis. In this study, we found that SUMOylation, a critical post-translational modification, is induced by a long-term treatment at warm temperatures via a SUMO ligase SIZ1 in Arabidopsis. Disruption of SIZ1 altered the global usage of polyadenylation signals and affected the APA dynamic of thermomorphogenesis-related genes. CPSF100, a key subunit of the CPSF complex for polyadenylation regulation, is SUMOylated by SIZ1. Importantly, we demonstrated that SUMOylation is essential for the function of CPSF100 in genome-wide polyadenylation site choice during thermomorphogenesis. Further analyses revealed that the SUMO conjugation on CPSF100 attenuates its interaction with two isoforms of its partner CPSF30, increasing the nuclear accumulation of CPSF100 for polyadenylation regulation. In summary, our study uncovers a regulatory mechanism of APA via SIZ1-mediated SUMOylation in plant thermomorphogenesis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Factor de Especificidad de Desdoblamiento y Poliadenilación , Regulación de la Expresión Génica de las Plantas , Poliadenilación , Sumoilación , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Factor de Especificidad de Desdoblamiento y Poliadenilación/metabolismo , Factor de Especificidad de Desdoblamiento y Poliadenilación/genética , Ligasas/metabolismo , Ligasas/genética , Vernalización
13.
Front Genet ; 13: 863253, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35559042

RESUMEN

Alternative polyadenylation (APA) of pre-mRNA is an important co-transcriptional mechanism that modulates gene expression, leading to transcriptomic and functional diversities. The role of APA in Arabidopsis leaf development, however, remains elusive. We applied a poly(A)-tag sequencing (PAT-seq) technique to characterize APA-mediated regulation events in cotyledon and in five stages of true leaf development. Over 60% APA was identified in genes expressed in leaves, consistent with the results in previous publications. However, a reduced APA level was detected in younger leaves, reaching 44% in the 18th true leaf. Importantly, we also found that >70% of the poly(A) site usages were altered in the second true leaf relative to the cotyledon. Compared with the cotyledon, more genes in the second true leaf tended to use the distal site of 3'UTR, but this was not found in pairwise comparison among other true leaves. In addition, a significant APA gene was found to be decreased in a pairwise comparison among true leaves, including differentially expressed genes. The APA genes identified herein were associated with specific biological processes, including metabolic and cellular processes and response to stimuli and hormones. These results provide a new insight into the regulation of Arabidopsis leaf development through APA.

14.
aBIOTECH ; 3(1): 49-64, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36304199

RESUMEN

With the increasing global warming, high-temperature stress is affecting plant growth and development with greater frequency. Therefore, an increasing number of studies examining the mechanism of temperature response contribute to a more optimal understanding of plant growth under environmental pressure. Post-translational modification (PTM) provides the rapid reconnection of transcriptional programs including transcription factors and signaling proteins. It is vital that plants quickly respond to changes in the environment in order to survive under stressful situations. Herein, we discuss several types of PTMs that occur in response to warm-temperature and high-temperature stress, including ubiquitination, SUMOylation, phosphorylation, histone methylation, and acetylation. This review provides a valuable resolution to this issue to enable increased crop productivity at high temperatures.

15.
Front Cell Infect Microbiol ; 11: 628275, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791238

RESUMEN

The Tripartite motif (TRIM) protein family, which contains over 80 members in human sapiens, is the largest subfamily of the RING-type E3 ubiquitin ligase family. It is implicated in regulating various cellular functions, including cell cycle process, autophagy, and immune response. The dysfunction of TRIMs may lead to numerous diseases, such as systemic lupus erythematosus (SLE). Lots of studies in recent years have demonstrated that many TRIM proteins exert antiviral roles. TRIM proteins could affect viral replication by regulating the signaling pathways of antiviral innate immune responses. Besides, TRIM proteins can directly target viral components, which can lead to the degradation or functional inhibition of viral protein through degradative or non-degradative mechanisms and consequently interrupt the viral lifecycle. However, new evidence suggests that some viruses may manipulate TRIM proteins for their replication. Here, we summarize the latest discoveries on the interactions between TRIM protein and virus, especially TRIM proteins' role in the signaling pathway of antiviral innate immune response and the direct "game" between them.


Asunto(s)
Antivirales , Virus , Humanos , Inmunidad Innata , Transducción de Señal , Proteínas de Motivos Tripartitos
16.
Artículo en Inglés | MEDLINE | ID: mdl-32202079

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects 0.5-1% of the world population. Current treatments include on one hand non-steroidal anti-inflammatory drugs and glucocorticoids (GCs) for treating pain and on the other hand disease-modifying anti-rheumatic drugs such as methotrexate, Janus kinase inhibitors or biologics such as antibodies targeting mainly cytokine expression. More recently, nucleic acids such as siRNA, miRNA, or anti-miRNA have shown strong potentialities for the treatment of RA. This review discusses the way nanomedicines can target GCs and nucleic acids to inflammatory sites, increase drug penetration within inflammatory cells, achieve better subcellular distribution and finally protect drugs against degradation. For GCs such a targeting effect would allow the treatment to be more effective at lower doses and to reduce the administration frequency as well as to induce much fewer side-effects. In the case of nucleic acids, particularly siRNA, knocking down proteins involved in RA, could importantly be facilitated using nanomedicines. Finally, the combination of both siRNA and GCs in the same carrier allowed for the same cell to target both the GCs receptor as well as any other signaling pathway involved in RA. Nanomedicines appear to be very promising for the delivery of conventional and novel drugs in RA therapeutics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.


Asunto(s)
Antirreumáticos , Artritis Reumatoide/tratamiento farmacológico , Glucocorticoides , Nanomedicina , Ácidos Nucleicos , Animales , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapéutico , Glucocorticoides/farmacocinética , Glucocorticoides/uso terapéutico , Humanos , Ratones , Ácidos Nucleicos/farmacocinética , Ácidos Nucleicos/uso terapéutico , ARN Interferente Pequeño , Ratas
17.
Clin Rheumatol ; 38(3): 657-664, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30280368

RESUMEN

To evaluate the efficacy and safety of total glucosides of peony (TGP) in adults with primary Sjögren's syndrome (pSS). A multi-center, randomized, double-blinded, placebo-controlled study was conducted between March 2012 and July 2014 at ten Chinese hospitals. In total, 320 pSS patients-classified according to the 2002 American-European Consensus Group Criteria-were randomized (2:1 ratio) to receive TGP(600 mg, tid) in the TGP group or placebo for 24 weeks in the placebo group. Study personnel, investigators, and patients were blinded to the treatment grouping. The primary endpoint was the improvement of EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 24. The secondary endpoints were dry eyes/mouth/skin/nose/throat/vagina visual analogue scale (VAS), pain and discomfort VAS, fatigue VAS, mental discomfort VAS, patient global assessment (PGA), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, basal/stimulated salivary flow-rate values, and erythrocyte sedimentation rate (ESR). All adverse events were recorded during the trial period. ESSPRI improved more in the TGP than the placebo group (p < 0.001). Dry eyes/throat/vagina VAS, fatigue VAS, mental discomfort VAS, PGA, Schirmer's test, and ESR also improved more in the TGP group than in the placebo group (all p < 0.05). Stimulated salivary flow-rate values increased in the TGP group at week 12 but not at week 24. Adverse events in TGP group were 10.9%. TGP can alleviate some dryness symptoms as well as disease activity in pSS patients over 24 weeks. TGP was well tolerated by study subjects. TGP seems to be an effective and safe treatment for pSS.


Asunto(s)
Paeonia , Fitoterapia , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Síndrome de Sjögren/tratamiento farmacológico , Adulto , Diarrea/inducido químicamente , Método Doble Ciego , Fatiga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Eliminación Salival , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/fisiopatología , Resultado del Tratamiento , Escala Visual Analógica
18.
Clin Rheumatol ; 38(2): 617-618, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30511293

RESUMEN

The authors regret that the Fig. 1 in the original version of this article contained an error. In the left column, 211 cases in the TGP group should be followed up for 8 weeks before 12 weeks. The correct figure presented in this article.

19.
Sci Total Environ ; 637-638: 233-243, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-29751306

RESUMEN

The objective of this study was to characterize the diversity and dynamics of rhizosphere bacterial community, especially the response of dominant and rare bacterial taxa to the cultivation of Bt cotton for different root environments at different growth stages. qPCR analyses indicated that bacterial abundances of the taproots and lateral root rhizospheres of the Bt cotton SGK321 were significantly different at seedling and bolling stages. But no significant differences were detected between the same root zones from Bt and the conventional cotton varieties. Total bacterial genera had similar pattern with dominant genera in abundance, and with rare genera in richness to the changes of bacterial community, respectively. Although the rhizosphere bacterial diversity of the three cotton varieties changed in taproot and lateral root, no significant differences were detected in the same root environments between Bt and conventional cotton. Moreover, Soil pH was more correlated with variations in the bacterial community composition than Bt proteins. In conclusion, these results revealed no indication that rhizosphere bacterial community of Bt cotton had different response to increased Bt protein regarding the same root environment. In particular, dominant and rare bacterial taxa showed the variation in diversity and community composition in different root microhabitats.


Asunto(s)
Biodiversidad , Monitoreo del Ambiente , Gossypium/genética , Plantas Modificadas Genéticamente/fisiología , Rizosfera , Microbiología del Suelo , Bacterias , Proteínas Bacterianas , Endotoxinas , Proteínas Hemolisinas , Suelo
20.
J Mater Chem B ; 5(21): 3810-3815, 2017 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-32264242

RESUMEN

Multifunctional 99mTc-labeled dendrimer-entrapped gold nanoparticles (99mTc-Au DENPs) were designed and synthesized. Our results show that the type of surface groups (acetyl or hydroxyl) significantly impact the biodistribution profile of the 99mTc-Au DENPs, thereby allowing for preferential SPECT/CT imaging of different organs.

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