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1.
Clin Rheumatol ; 43(6): 1855-1863, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704780

RESUMO

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.


Assuntos
Artrite Reumatoide , Biomarcadores Tumorais , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/etiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Idoso , Biomarcadores/sangue , Curva ROC , Modelos Logísticos , Queratina-19/sangue , Adulto , Proteína C-Reativa/análise , Índice de Gravidade de Doença , Antígeno CA-19-9/sangue , Antígenos de Neoplasias
2.
Clin Exp Rheumatol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530663

RESUMO

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.

3.
Sci Rep ; 14(1): 5783, 2024 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461210

RESUMO

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.


Assuntos
Doenças Autoimunes , Síndrome de Guillain-Barré , Síndrome de Sjogren , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Guillain-Barré/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Sjogren/diagnóstico , Autoanticorpos , Doenças Autoimunes/tratamento farmacológico
4.
Biomacromolecules ; 24(2): 667-677, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36599673

RESUMO

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.


Assuntos
Artrite Experimental , Dendrímeros , Animais , Camundongos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Fator de Necrose Tumoral alfa/genética , Anti-Inflamatórios/farmacologia
5.
Plant Physiol ; 191(3): 1871-1883, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36464768

RESUMO

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.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Transdução de Sinais , Sumoilação , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
6.
aBIOTECH ; 3(1): 49-64, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36304199

RESUMO

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.

7.
Front Genet ; 13: 863253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559042

RESUMO

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.

8.
RNA Biol ; 18(12): 2594-2604, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34036876

RESUMO

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.


Assuntos
Arabidopsis/genética , Poliadenilação , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , RNA de Plantas/genética , Transcrição Gênica , Transcriptoma
9.
Front Cell Infect Microbiol ; 11: 628275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791238

RESUMO

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.


Assuntos
Antivirais , Vírus , Humanos , Imunidade Inata , Transdução de Sinais , Proteínas com Motivo Tripartido
10.
Artigo em Inglês | MEDLINE | ID: mdl-32202079

RESUMO

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.


Assuntos
Antirreumáticos , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides , Nanomedicina , Ácidos Nucleicos , Animais , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapêutico , Glucocorticoides/farmacocinética , Glucocorticoides/uso terapêutico , Humanos , Camundongos , Ácidos Nucleicos/farmacocinética , Ácidos Nucleicos/uso terapêutico , RNA Interferente Pequeno , Ratos
11.
Plant Cell ; 31(10): 2332-2352, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31427469

RESUMO

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.


Assuntos
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Poliadenilação/genética , Sinais de Poliadenilação na Ponta 3' do RNA/genética , RNA Mensageiro/genética , Transcriptoma/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo , Regiões 3' não Traduzidas/genética , Fator de Especificidade de Clivagem e Poliadenilação/genética , Flores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Ontologia Genética , Redes Reguladoras de Genes , Mutação , Fenótipo , Raízes de Plantas/metabolismo , Ligação Proteica , Domínios Proteicos/genética , Repetições WD40/genética
12.
Clin Rheumatol ; 38(3): 657-664, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30280368

RESUMO

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.


Assuntos
Paeonia , Fitoterapia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Síndrome de Sjogren/tratamento farmacológico , Adulto , Diarreia/induzido quimicamente , Método Duplo-Cego , Fadiga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Eliminação Salivar , Índice de Gravidade de Doença , Síndrome de Sjogren/fisiopatologia , Resultado do Tratamento , Escala Visual Analógica
13.
Clin Rheumatol ; 38(2): 617-618, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30511293

RESUMO

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.

14.
Sci Total Environ ; 637-638: 233-243, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29751306

RESUMO

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.


Assuntos
Biodiversidade , Monitoramento Ambiental , Gossypium/genética , Plantas Geneticamente Modificadas/fisiologia , Rizosfera , Microbiologia do Solo , Bactérias , Proteínas de Bactérias , Endotoxinas , Proteínas Hemolisinas , Solo
15.
Front Behav Neurosci ; 11: 124, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28701932

RESUMO

Objective: The objective of this study was to investigate resting-state functional connectivity (FC) differences in insular sub-regions during the interictal phase in patients with migraine without aura (MWoA). Methods: Forty-nine MWoA patients (MWoA group) and 48 healthy individuals (healthy control group) were recruited for this study. All of the subjects underwent neurological examination and magnetic resonance imaging (MRI). The MRI data were processed using Brat 1.0 software to obtain a whole-brain FC diagram and using Rest 1.8 software to obtain the FC z-score of the sub-regions of both insulas (six sub-regions on each side). Therefore, there were a total of 12 regions of interest (ROIs) that were used as seed points for the statistical analysis. Results: There was abnormal FC between the insular sub-regions and multiple brain regions in the MWoA patients compared with the healthy control group, and a clear laterality was also observed. In addition, the FC z-score of certain sub-regions was negatively correlated with the disease duration. Conclusion: Different insular sub-regions are functionally associated with different regions of the brain and therefore have different functions. In MWoA, the FC between the insular sub-regions and other brain regions was mostly reduced, while a small amount was increased; additionally, the FC may be ipsilateral with a right-side advantage. Variations in the FC of insular sub-regions can be observed as an important indicator of MWoA.

16.
J Mater Chem B ; 5(21): 3810-3815, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264242

RESUMO

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.

17.
Medicine (Baltimore) ; 95(37): e4824, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27631235

RESUMO

The results of neuroimaging studies on migraines have shown that the functions and functional connectivity networks of some brain regions are altered in migraine patients, and different brain structure volumes have also been observed in recent years. However, it is still not known whether the mean thickness of the cortex is different in migraine patients.A total of 48 migraine without aura (MWoA) patients in interictal phase and 48 healthy controls were enrolled in this study. All subjects received neurological and magnetic resonance imaging (MRI) examinations. Automatic segmentation processing of high-resolution MRI structure images was performed using FreeSurfer software.The mean cortical thickness of many brain regions in the frontal lobe, temporal lobe, occipital lobe, parietal lobe, and insula in the migraine patient group was significantly decreased compared with that in the healthy control group. The mean cortical thickness of the insula anterior was positively correlated with the duration of the disease course, while the mean cortical thickness of insula superior and insula inferior was negatively correlated with the duration of the disease course.The results showed that MWoA results from a complex interactive reaction involving many brain regions and many brain network systems together. However, it is still not clear whether the difference in the brain structure of migraine patients is the result or the cause of headache, which is a topic that must be better elucidated. Therefore, longitudinal neuroimaging studies on migraine patients with large samples sizes should be performed using more advanced neuroimaging techniques.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Enxaqueca sem Aura/diagnóstico por imagem , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Neuroscience ; 330: 90-9, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-27208615

RESUMO

Previous studies have shown that iron redistribution and deposition in the brain occurs in some neurodegenerative diseases, and oxidative damage due to abnormal iron level is a primary cause of neuronal death. In the present study, we used the single prolonged stress (SPS) model to mimic post-traumatic stress disorder (PTSD), and examined whether iron was involved in the progression of PTSD. The anxiety-like behaviors of the SPS group were assessed by the elevated plus maze (EPM) and open field tests, and iron levels were measured by inductively coupled plasma optical emission spectrometer (ICP-OES). Expression of glucocorticoid receptors and transferrin receptor 1 (TfR1) and ferritin (Fn) was detected by Western blot and immunohistochemistry in selected brain areas; TfR1 and Fn mRNA expression were detected by quantitative-polymerase chain reaction (Q-PCR). Ultrastructures of the hippocampus were observed under a transmission electron microscope. Our results showed that SPS exposure induced anxiety-like symptoms and increased the level of serum cortisol and the concentration of iron in key brain areas such as the hippocampus, prefrontal cortex, and striatum. The stress induced region-specific changes in both protein and mRNA levels of TfR1 and Fn. Moreover, swelling mitochondria and cell apoptosis were observed in neurons in brain regions with iron accumulation. We concluded that SPS stress increased iron in some cognition-related brain regions and subsequently cause neuronal injury, indicating that the iron may function in the pathology of PTSD.


Assuntos
Encéfalo/metabolismo , Ferro/metabolismo , Neurônios/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/patologia , Apoptose/fisiologia , Encéfalo/patologia , Modelos Animais de Doenças , Ferritinas/metabolismo , Hidrocortisona/sangue , Ferro/toxicidade , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neurônios/patologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo , Receptores da Transferrina/metabolismo , Transtornos de Estresse Pós-Traumáticos/patologia
19.
Biomater Sci ; 4(3): 474-82, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26730414

RESUMO

We report the synthesis, characterization and utilization of LAPONITE®-stabilized magnetic iron oxide nanoparticles (LAP-Fe3O4 NPs) as a high performance contrast agent for in vivo magnetic resonance (MR) detection of tumors. In this study, Fe3O4 NPs were synthesized by a facile controlled coprecipitation route in LAP solution, and the formed LAP-Fe3O4 NPs have great colloidal stability and about 2-fold increase of T2 relaxivity than Fe3O4 NPs (from 247.6 mM(-1) s(-1) to 475.9 mM(-1) s(-1)). Moreover, cytotoxicity assay and cell morphology observation demonstrate that LAP-Fe3O4 NPs display good biocompatibility in the given Fe concentration range, and in vivo biodistribution results prove that NPs can be metabolized and cleared out of the body. Most importantly, LAP-Fe3O4 NPs can not only be used as a contrast agent for MR imaging of cancer cells in vitro due to the effective uptake by tumor cells, but also significantly enhance the contrast of a xenografted tumor model. Therefore, the developed LAP-based Fe3O4 NPs with good colloidal stability and exceptionally high transverse relaxivity may have tremendous potential in MR imaging applications.


Assuntos
Compostos Férricos/síntese química , Nanopartículas/química , Silicatos/síntese química , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Compostos Férricos/química , Humanos , Imageamento por Ressonância Magnética/métodos , Magnetismo , Teste de Materiais , Polietilenoimina/química , Silicatos/química
20.
Physiol Plant ; 156(3): 311-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26294083

RESUMO

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.


Assuntos
Pressão Osmótica , Homologia de Sequência de Aminoácidos , Solanum lycopersicum/enzimologia , Estresse Fisiológico , Vitamina K Epóxido Redutases/metabolismo , Adaptação Fisiológica , Antioxidantes/metabolismo , Secas , Escherichia coli/metabolismo , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Solanum lycopersicum/genética , Viabilidade Microbiana , Plantas Geneticamente Modificadas , RNA Antissenso/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Superóxidos/metabolismo
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