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1.
Artículo en Inglés | MEDLINE | ID: mdl-36768042

RESUMEN

When considering how to improve public literacy and behavior related to specific themes, top priority is usually given to strategies that enhance relevant knowledge. Fostering attitude comes later. Understanding the mechanisms of behavior may help us develop better policy and educational strategies. However, how knowledge and attitude impact behavior is still under investigation. The aim of this study is to explore the relationships among ocean knowledge, attitude toward the ocean, and the intention to behave responsibly in the marine setting. Specifically, we investigated a potential mediation mechanism by recruiting a total of 266 participants, whose ocean knowledge, attitudes toward the ocean, and intention to behave responsibly were evaluated using questionnaires. The results indicate that a person's attitude toward the ocean may indeed be a mediating factor between ocean knowledge and their intention to show positive marine behavior. In order to engage people in responsible ocean behavior, other forms of assistance from marine policy and education are recommended. Additionally, it would be of interest for future studies to investigate the effects of attitude and attitude-related knowledge in the development of ocean actions.


Asunto(s)
Actitud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Intención , Encuestas y Cuestionarios , Escolaridad , Océanos y Mares
2.
Rheumatology (Oxford) ; 62(3): 1087-1096, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35946529

RESUMEN

OBJECTIVE: The most used drug for the treatment of rheumatoid arthritis (RA) remains methotrexate (MTX). Unfortunately, up to 50% of patients do not achieve a clinically adequate outcome. Here we study whether the gut microbiota patterns can aid in the prediction of MTX efficacy for RA. METHOD: To dissect gut microbiome profiles of RA patients (n = 145), 16S rRNA gene sequencing was performed. Dirichlet multinomial mixture (DMM) clustering was used to identify enterotypes at genus level. The relationships between enterotypes and clinical measures (such as lymphocyte subsets and cytokines detected by flow cytometry) were explored. Then, enterotype stability was evaluated by the stratification of the RA patient cohort (n = 66) in Shanghai, China, using the same method. Finally, the enterotype-based gut microbial human index classifier was applied to another independent RA patient cohort (n = 27) to identify the factors associated with MTX clinical response. RESULTS: Our analysis revealed that the RA patients always displayed two different dysbiotic microbiota patterns: RA E1 comprised predominantly Prevotella and RA E2 comprised predominantly Bacteroides. Among all of the lymphocyte subsets and cytokines, only the number of CD8+ T cells showed a significant difference between RA E1 and RA E2. These results were validated in the RA patient cohort in Shanghai, China. Significant associations of RA E1 with clinical response to subsequent MTX treatment were confirmed by another independent RA patient cohort. CONCLUSION: Together, the enterotype-based gut microbial human index (EGMI) classifier was useful to precisely and effectively identify enterotypes of individual RA patients, which could effectively evaluate MTX clinical responses.


Asunto(s)
Artritis Reumatoide , Microbioma Gastrointestinal , Humanos , Metotrexato/uso terapéutico , ARN Ribosómico 16S/genética , China , Artritis Reumatoide/tratamiento farmacológico , Citocinas
3.
Front Immunol ; 13: 939265, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35967336

RESUMEN

Anti-citrullinated protein antibodies (ACPAs) are highly specific for the diagnosis of rheumatoid arthritis (RA). However, about one-third of RA patients are negative for ACPAs, which presents a challenge to the early diagnosis of RA. The purpose of this study was to analyze differences in lymphocyte subsets and CD4+ T cell subsets between ACPA+ and ACPA- RA patients, and to evaluate the value of matrix metalloproteinase-3 (MMP-3) as a diagnostic and monitoring marker in ACA- RA patients. A total of 145 ACPA+ RA patients, 145 ACPA- RA patients, and 38 healthy controls (HCs) were included in this study. Peripheral lymphocyte subsets were detected using flow cytometry, and serum MMP-3 was detected using chemiluminescence. Information about joint symptoms, other organ involvement, and related inflammatory markers was also collected. The results showed that, compared to ACPA- RA patients, ACPA+ cases had greater imbalances between peripheral CD4+ T cell subsets, mainly manifested as an increase in T-helper 1 (Th1) cells (p < 0.001) and decrease in regulatory T (Treg) cells (p = 0.029). This makes these patients more prone to inflammatory reactions and joint erosion. MMP-3 levels in ACPA+ and ACPA- RA patients were significantly higher than in HCs (p < 0.001), and MMP-3 could effectively distinguish between ACPA- RA patients and HCs (area under the curve [AUC] = 0.930, sensitivity 84.14%, specificity 92.11%). MMP-3 was also a serum marker for distinguishing between RA patients with low and high disease activities. Further analysis showed that MMP-3 was positively correlated with the levels of inflammatory markers and disease activity, and negatively correlated with the levels of lymphocyte subsets. In addition, with improvements in the disease, MMP-3 levels decreased, and further increased as the patients started to deteriorate. In summary, our research showed that there was a mild imbalance between peripheral CD4+ T cell subsets in ACPA- RA patients. MMP-3 may be used as a potential marker for early diagnosis of ACPA- RA. MMP-3 was an important index for RA disease evaluation, disease activity stratification, and prognosis.


Asunto(s)
Artritis Reumatoide , Metaloproteinasa 3 de la Matriz/metabolismo , Anticuerpos Antiproteína Citrulinada , Autoanticuerpos , Biomarcadores , Humanos , Mieloblastina
4.
Arthritis Res Ther ; 24(1): 121, 2022 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-35606782

RESUMEN

OBJECTIVE: Primary Sjogren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands and the involvement and dysfunction of multiple organs and tissues. Interstitial lung disease (ILD) is the most common type of respiratory system damage. This study ascertained the factors related to ILD in patients with pSS (pSS-ILD), such as altered levels of circulating lymphocyte subtypes. METHODS: Eighty healthy controls and 142 patients diagnosed with pSS were included. The pSS patients were classified into groups with pSS-ILD or pSS without ILD (pSS-non-ILD). Baseline clinical and laboratory data were collected for all subjects, including the levels of lymphocytes measured by modified flow cytometry. RESULTS: The pSS-ILD patients were older, had higher ESSDAI scores, had higher positivity rates for anti-SSB and anti-Ro52 antibodies, and had more frequent symptoms of respiratory system involvement than pSS-non-ILD patients. pSS-ILD patients had the lowest Th2 cell counts among the three groups. Although the absolute numbers of Treg and NK cells were lower in pSS patients with and without ILD than in the healthy controls, there was no significant difference between the two pSS groups. The Th1/Th2 ratio was significantly higher in patients with ILD than in patients without ILD. Further analysis showed that older age (OR=1.084), lower Th2 count (OR=0.947), higher Th1/Th2 ratio (OR=1.021), and positivity for anti-SSB (OR=3.620) and anti-Ro52 (OR=5.184) antibodies were associated with the occurrence of ILD in patients with pSS. CONCLUSION: Decreased circulating Th2 cells and an elevated Th1/Th2 ratio may be the immunological mechanism underlying the development of ILD in pSS patients.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Síndrome de Sjögren , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Linfocitos , Estudios Retrospectivos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Células Th2
5.
Adv Ther ; 39(7): 3280-3291, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35604524

RESUMEN

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease characterized by synovial inflammation with unknown aetiology. Immune system dysfunction mediated by CD4+ T lymphocytes, which is regulated by the cytokine osteopontin (OPN), plays an important role in the pathogenesis of RA. METHODS: In this study, the levels of peripheral CD4+ T subsets and serum OPN in patients with active RA were measured and analysed to determine the possible pathogenesis of RA and to provide potential therapeutic targets. RESULTS: Serum OPN levels in both patients with active RA and patients with refractory RA were higher than those in healthy controls (HCs). Compared with HCs, the absolute numbers of Th2 cells increased in patients with active RA, while the absolute counts of Th1 and Treg cells decreased. There was no significant difference in CD4+ T subset levels between new-onset and refractory patients. As the condition persisted or deteriorated, a gradual increase in the levels of OPN and gradual declines in the absolute counts of Th1 and Treg cells were observed in patients with active RA. The fewest Th1 and Treg cells and the highest OPN levels were observed in patients with high disease activity. The serum OPN level was only significantly negatively correlated with the absolute counts of Treg cells in the CD4+ T lymphocyte subsets. CONCLUSIONS: Fewer Treg cells with the increase in disease activity may be related to the increased OPN concentration, which may provide new ideas and directions for the targeted immunoregulatory treatment of RA.


Asunto(s)
Artritis Reumatoide , Osteopontina , Linfocitos T Reguladores , Artritis Reumatoide/tratamiento farmacológico , Citocinas , Progresión de la Enfermedad , Humanos , Osteopontina/uso terapéutico , Linfocitos T
6.
Rheumatol Ther ; 9(4): 1049-1059, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35499817

RESUMEN

INTRODUCTION: Osteoporosis (OP) is one of the major comorbidities of rheumatoid arthritis (RA). Recent studies have shown that immune cells modulate bone health and regulate bone remodeling. However, the alterations of lymphocyte subsets in RA patients with OP are unclear. Here, we assessed the absolute numbers and proportions of the subsets in RA sufferers with OP and investigated the clinical significance. METHODS: A total of 777 RA patients and 117 gender- and age-matched healthy controls (HCs) were enrolled in this study. Patients were divided into RA-non-OP and RA-OP group according to their bone mineral density (BMD) and the history of fragility fracture. Peripheral lymphocyte subsets of participants were assessed by flow cytometry. RESULTS: Among 220 (28.31%) RA-OP patients, there were higher levels of erythrocyte sedimentation rate (ESR) (P = 0.011), C-reactive protein (CRP) (P = 0.028), rheumatoid factor (RF) (P = 0.013) and anti-cyclic citrullinated peptide antibody (ACPA) (P = 0.010), while red blood cells (RBC) (P = 0.039) were lower than those in RA-non-OP group. Compared with those of HCs and RA-non-OP group, the level of circulating Th17 cells in RA-OP patients was significantly increased (P < 0.05), while those of Tregs decreased (P < 0.01), leading to a higher ratio of Th17/Treg (P < 0.01). Notably, the level of B cells in both RA-non-OP and RA-OP group was reduced, this alteration was more obvious in patients with OP (P < 0.05). CONCLUSIONS: Immune disorders characterized by peripheral Th17/Treg imbalance and reduced B cells may contribute directly or indirectly to OP in RA, and this deserves more clinical attention.

7.
Mol Immunol ; 147: 90-100, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35523039

RESUMEN

BACKGROUND: Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands. The current study was performed to investigate the roles of follicular helper T (Tfh) and follicular regulatory T (Tfr) subsets in patients with pSS, and to evaluate the effects of sirolimus on these cells. METHODS: Levels of circulating Tfh and Tfr subsets in 58 pSS patients and 26 healthy controls (HC) were determined by flow cytometry. These T cell subsets were also analyzed in 12 patients before and after treatment with sirolimus. Clinical features and correlations with follicular T cells were analyzed systematically. The discriminative ability of the cells and ratios was evaluated based on the area under the receiver operating characteristic curves. RESULTS: Patients with pSS had higher percentage and absolute number of PD-1+ICOS+Tfh cells, while lower percentage and absolute number of Tfr, activated regulatory T (aTreg) cells, and CD45RA-Foxp3high activated Tfr cells. Furthermore, increased number of PD-1+ICOS+Tfh cells was associated with B cells, while decreased numbers of Tfr and their subsets was strongly associated with aTreg cells in pSS patients. Also, the higher proportion of PD-1+ICOS+Tfh cells was positively correlated with higher level of autoantibodies, ESR, IgG, cytokines (IL-2, IL-4, IL-10, IL-17, IFN-γ, TNF-α, IL-21 and sIL-2αR), and disease activity. Unexpectedly, the elevated PD-1+ICOS+Tfh:CD45RA-Foxp3high activated Tfr ratio had the greatest ability to discriminate between pSS and HC, and sirolimus therapy restored the PD-1+ICOS+Tfh cells:CD45RA-Foxp3high activated Tfr ratio, and controlled disease activity. CONCLUSION: The novel ratio of PD-1+ICOS+Tfh to CD45RA-Foxp3high activated Tfr cells can effectively discriminate the pSS patients from controls, and Tfr cell subsets may resemble Treg cell lineages. Furthermore, the PD-1+ICOS+Tfh cells can be used as a biomarker of disease activity and to verify the therapeutic effects of sirolimus in pSS.


Asunto(s)
Síndrome de Sjögren , Células T Auxiliares Foliculares , Factores de Transcripción Forkhead , Humanos , Proteína Coestimuladora de Linfocitos T Inducibles , Antígenos Comunes de Leucocito , Receptor de Muerte Celular Programada 1 , Sirolimus/uso terapéutico , Síndrome de Sjögren/tratamiento farmacológico , Linfocitos T Colaboradores-Inductores , Linfocitos T Reguladores
8.
Org Biomol Chem ; 20(7): 1500-1509, 2022 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-35107479

RESUMEN

A general and practical method for the synthesis of α,α-difluoro(arylthio)methyl oxetanes that occurs by the reaction of α,α-difluoro(arylthio)methyl ketones with trimethylsulfoxonium halides is reported. This reaction proceeds via the sequential Corey-Chaykovsky epoxidation and regioselective ring-expansion pathways and features mild conditions, operational simplicity, gram-scalability, a broad substrate scope and high yields. α,α-Difluoro(arylthio)methyl oxiranes have been shown to be the reaction intermediates. The obtained α,α-difluoro(arylthio)methyl oxetanes were further converted into useful sulfone, butenolide, and tetrahydrofuran derivatives.

9.
Front Immunol ; 12: 744254, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34721413

RESUMEN

Patients with rheumatoid arthritis (RA) have a significantly high risk of atrial fibrillation (AF). This study aimed to compare the absolute and relative changes in peripheral T cells in patients with RA who were also affected with and without AF. To help make an early diagnosis and prevent the initiation and progression of AF, the changes in the lymphocyte subsets were assessed in RA patients with and without AF. A propensity score matching (PSM) system (1:3) was used to perform a matched case-control study with 40 RA-AF cases and 120 RA controls. Changes in the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-citrullinated peptide antibody (ACPA), and rheumatoid factor (RF) were examined. The percentage and absolute number of T, B, natural killer (NK), T helper (Th)1, Th2, Th17, and T-regulatory (Treg) cells in the peripheral blood of patients with and without RA-AF were determined using flow cytometry. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-AF. Demographic data, ESR, CRP, ACPA, and the percentage, as well as the absolute value of B, NK, Th2, and Treg cells, showed no significant differences between the propensity score-matched groups of RA and RA-AF. Meanwhile, the absolute number and percentage of Th1 cells, the absolute number of Th17 cells, the ratio of Th1/Treg, Th17/Treg, and RF were significantly higher in patients with RA-AF than those in the control groups (P < 0.05). Univariate and multivariate logistic regression analyses also revealed that the percentage of Th1 cells, the absolute number of Th17 cells, and the ratio of Th1/Treg were associated with a significantly higher risk of AF. This PSM study demonstrated that the incidence of AF was higher in RA patients with Th cell immunological derangements.


Asunto(s)
Artritis Reumatoide/inmunología , Fibrilación Atrial/epidemiología , Fibrilación Atrial/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Anciano , Artritis Reumatoide/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos
10.
Ther Adv Musculoskelet Dis ; 13: 1759720X211011370, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33995604

RESUMEN

BACKGROUND: Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4+T subsets and the clinical feasibility of IL-2 therapies in patients with RA. METHODS: The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment. RESULTS: RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs (p < 0.05). Patients treated with low-dose IL-2 had a three-fold increase in absolute anti-inflammatory Treg counts, as well as a two-fold increase in the other CD4+T subsets. Moreover, post-treatment levels of markers of disease activity in RA patients treated with IL-2 were significantly lower than the baseline values (p < 0.001), with no apparent side effects. CONCLUSION: Decreased absolute counts of circulating CD4+T lymphocyte subsets were observed in patients with RA. Circulating Tregs, which mediate immune tolerance, may be involved in the pathogenesis and progression of RA; however, this was ameliorated by low-dose IL-2, without obvious side effects. PLAIN LANGUAGE SUMMARY: Low-dose IL-2 treatment for rheumatoid arthritis • Circulating Tregs may be involved in the pathogenesis and progression of RA.• The absolute count of Tregs was significantly correlated with disease activity measures.• Low-dose IL-2 was able to effectively expade Tregs and help for RA patients' symptoms remission without evaluated side effects.

11.
Plant Dis ; 105(9): 2466-2471, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33529065

RESUMEN

Cereal cyst nematode (Heterodera avenae), an important plant-parasitic nematode causing yield losses of wheat, has been found in many provinces in China. It is urgent to develop an effective method of protecting wheat from H. avenae damage. Because of its novel mode of action, fluopyram has been registered for controlling root-knot nematodes on cucumber and tomato in China. However, the bioactivity of fluopyram against H. avenae and whether this seed treatment can effectively control H. avenae on wheat remains unknown. In this study, a bioactivity assay revealed that fluopyram increased the mortality of H. avenae second-stage juveniles (J2), with lethal concentrations (LC) required to kill 50% (LC50) and 90% (LC90) of 0.92 mg⋅liter-1 and 2.92 mg⋅liter-1, respectively. Hatching tests showed that the H. avenae egg hatching percent was reduced by 35.2 to 69.2% with fluopyram at rates of 1.6 to 6.4 mg⋅liter-1, and that the egg hatching period was delayed by 3 to 9 days compared with the control. During pot and field trials, fluopyram seed treatment significantly reduced the H. avenae population density and increased wheat yield by 3.0 to 13.7%. Therefore, fluopyram seed treatment is an effective approach for the management of H. avenae on wheat in China.


Asunto(s)
Quistes , Tylenchoidea , Animales , Benzamidas , Grano Comestible , Piridinas , Semillas , Triticum
12.
Front Immunol ; 12: 768244, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35006213

RESUMEN

Background: Takayasu's arteritis (TA) is a type of primary large vessel vasculitis. Th1, Th17, and Tfh cells have been reported to be associated with TA relapse. However, the relationship between regulatory T cells (Tregs) and TA remains unclear. Objective: To analyze the levels of circulating lymphocytes, especially Treg cells (CD4+CD25+FOXP3+ T cells) and serum cytokines in TA patients and explore their relationship with their changes and TA disease activity. Methods: A total of 57 TA patients and 43 sex- and age-matched healthy controls (HCs) were enrolled. According to NIH standards, 36 patients had active disease status. Flow cytometry combined with counting was used to detect the absolute numbers and ratios of Th1, Th2, Th17, and Treg cells in the peripheral blood of all the subjects. Magnetic bead-based multiplex immunoassay was used to detect cytokines. Results: Compared to HCs, the absolute number and proportion of peripheral Treg cells in TA patients was significantly decreased, while Th17 cells were significantly increased. Furthermore, compared to the inactive group, the TA active group had significantly increased levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α, but lower IL-10 levels. The absolute number of Th2 cells was negatively associated with platelet (PLT) and NIS scores in TA patients. The proportion of Th2 cells was negatively associated with the erythrocyte sedimentation rate in TA patients. After treatment, Treg cells were markedly increased. Conclusion: There was a Th17-Treg cell imbalance with a significant reduction in peripheral Treg cells and an increase in Th17 cells in TA patients compared to the HCs. The levels of IL-6, IL-10, IL-17, and TNF-α appeared to be related to disease activity.


Asunto(s)
Linfocitos T Reguladores/inmunología , Arteritis de Takayasu/inmunología , Adolescente , Adulto , Sedimentación Sanguínea , Citocinas/biosíntesis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Células Th2/inmunología , Adulto Joven
14.
Cytokine ; 136: 155251, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32828065

RESUMEN

Patients with rheumatoid arthritis (RA) are more susceptible to infections, which elevate the levels of relative cytokines. However, the ability of the cytokines levels to predicate bacterial infections in RA patients remains unclear. Here, we assessed the ability of the combination of serum cytokine levels and blood parameters to diagnose bacterial infections in RA patients. We measured the levels of a panel of serum cytokine and blood parameters in 168 RA patients and 81 healthy individuals. RA patients were divided into the bacterial infection (INFE) group (n = 76) and RA flare without INFE group (n = 92). Bacterial infection was confirmed by microbial culture, imaging, antibiotic response, and typical clinical symptoms. The discriminative ability of the combination of the cytokine levels and inflammatory parameters was assessed using the receiver-operating characteristic (ROC) curves analysis and a novel bioscore system. The levels of interleukin (IL)-6 (p = 0.006), IL-10 (p = 0.019), interferon (IFN)-γ (p = 0.033), CRP (p < 0.001), and ESR (p < 0.001) were higher in patients of the INFE group than in patients with RA flare, and the absolute numbers of CD19+ B cells (p < 0.001) and CD4+ T cells (p = 0.009) were lower. For discriminating bacterial infection, the combination of IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells, and CD4+ T cells, provided an area under the curve (AUC) of 0.827 [(95% confidence interval (CI): 0.760-0.881)], which was profoundly larger than that of IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells, or CD4+ T cells alone. In addition, we also developed a bioscore system based on the combination of these seven biomarkers. Seventeen (100%) patients with a bioscore of 0 were non-infected, while seven (100%) patients with a score of 7 had bacterial infections. The bioscore based on the combination of ESR, CRP, IL-6, IL-10, IFN-γ, CD19+ B cells and CD4+ T cells may be a promising and robust tool to diagnose bacterial infections in RA patients.


Asunto(s)
Artritis Reumatoide , Linfocitos B/metabolismo , Infecciones Bacterianas , Linfocitos T CD4-Positivos/metabolismo , Citocinas/sangre , Adulto , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/microbiología , Infecciones Bacterianas/sangre , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Nat Commun ; 11(1): 4112, 2020 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-32807784

RESUMEN

Macropinocytosis is essential for myeloid cells to survey their environment and for growth of RAS-transformed cancer cells. Several growth factors and inflammatory stimuli are known to induce macropinocytosis, but its endogenous inhibitors have remained elusive. Stimulation of Roundabout receptors by Slit ligands inhibits directional migration of many cell types, including immune cells and cancer cells. We report that SLIT2 inhibits macropinocytosis in vitro and in vivo by inducing cytoskeletal changes in macrophages. In mice, SLIT2 attenuates the uptake of muramyl dipeptide, thereby preventing NOD2-dependent activation of NF-κB and consequent secretion of pro-inflammatory chemokine, CXCL1. Conversely, blocking the action of endogenous SLIT2 enhances CXCL1 secretion. SLIT2 also inhibits macropinocytosis in RAS-transformed cancer cells, thereby decreasing their survival in nutrient-deficient conditions which resemble tumor microenvironment. Our results identify SLIT2 as a physiological inhibitor of macropinocytosis and challenge the conventional notion that signals that enhance macropinocytosis negatively regulate cell migration, and vice versa.


Asunto(s)
Citoesqueleto/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Receptores Inmunológicos/metabolismo , Animales , Quimiocina CXCL1/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Péptidos y Proteínas de Señalización Intercelular/genética , Macrófagos/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Proteínas del Tejido Nervioso/genética , Fagocitos/metabolismo , Pinocitosis/genética , Pinocitosis/fisiología , Receptores Inmunológicos/genética , Transducción de Señal/genética , Transducción de Señal/fisiología , Proteína de Unión al GTP rhoA/metabolismo , Proteínas Roundabout
16.
J Int Med Res ; 48(7): 300060520913149, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32649852

RESUMEN

OBJECTIVE: To guide clinical decision making, race-, age- and gender-specific reference ranges for lymphocytes and CD4+ T-cell subsets are required. METHODS: Single platform flow cytometry to determine reference intervals for lymphocyte subpopulations and CD4+ T-cell subsets in 196 healthy Han Chinese adults. RESULTS: The frequencies and absolute numbers of B cells were slightly lower in Han Chinese individuals of the Shanxi region than in individuals from Hong Kong, Germany and Singapore, while percentages and absolute numbers of NK cells were slightly higher compared with individuals from Hong Kong. CD4+/CD8+ T-cell ratios, CD4+ T cell percentages and Th2 cell counts were higher, while frequencies and numbers of CD8+ T cells, numbers of NK cells and percentages of Th1 cells were lower, in females compared with males. CD4+ T cell percentages, CD4+/CD8+ T-cell ratios, numbers of CD8+ T cells and Treg cells, and Th17/Treg cell ratios differed by age. CONCLUSION: We established lymphocyte and CD4+ T-cell subset reference intervals for healthy Han Chinese adults of the Shanxi region. Ethnicity, gender and age affected lymphocyte subset composition.


Asunto(s)
Linfocitos T CD4-Positivos , Subgrupos de Linfocitos T , Adulto , China , Femenino , Citometría de Flujo , Alemania , Humanos , Recuento de Linfocitos , Masculino , Valores de Referencia
17.
Clin Biochem ; 83: 43-48, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32502475

RESUMEN

BACKGROUND: The goal of this study was to investigate the association between bactericidal permeability increasing (BPI)-antineutrophil cytoplasmic antibody (ANCA) protein levels and primary Sjogren's syndrome (pSS) with lung involvement, as well as the potential diagnostic performance of BPI-ANCA. METHODS: The levels of BPI-ANCA in pSS patients with (n = 36) and without (n = 85) lung involvement were measured using a commercial ELISA kit. Serological biomarkers and cytokines were measured in these patients as well. Lung involvement was determined by high-resolution computed tomography (HRCT) and/or clinical symptoms. The diagnostic performance of lung involvement was determined by receiver operating characteristic (ROC) curves. RESULTS: The percentage of neutrophils (NEUT%), neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), and the levels of BPI-ANCA, C-reactive protein (CRP), interleukin-2 (IL-2) and IL-6 exhibited an upward trend, while the percentage of lymphocytes (LYMP%) and albumin (ALB) level exhibited a downward trend in the lung involvement group. The combination of BPI-ANCA, NEUT% and ALB significantly increased the area under the ROC curve (AUC) to 0.837 (95% confidence interval: 0.742-0.907, sensitivity: 82.14%, specificity: 81.36%, P < 0.001). CONCLUSIONS: Increased BPI-ANCA was found in pSS patients with lung involvement and was associated with inflammation. A combination of BPI-ANCA, NEUT% and ALB had the best AUC, and may serve as anadjunct to distinguish between pSS patients with and without lung involvement.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Péptidos Catiónicos Antimicrobianos/inmunología , Proteínas Sanguíneas/inmunología , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/complicaciones , Síndrome de Sjögren/sangre , Síndrome de Sjögren/complicaciones , Adulto , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Biomarcadores , Estudios de Casos y Controles , Citocinas/sangre , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Síndrome de Sjögren/inmunología
18.
Pest Manag Sci ; 76(6): 2217-2224, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31970922

RESUMEN

BACKGROUND: Root-knot nematodes (Meloidogyne spp.) are soilborne pathogens that can cause great damage to and economic loss of crops globally. Owing to the high toxicity of chemicals toward humans and the environment, the use of biocontrol bacteria, a promising method for controlling root-knot nematodes, has gained attention. RESULTS: To screen novel bacterial strains for their ability to control root-knot nematodes, 106 bacterial strains were isolated from soil. Eight of the obtained isolates exhibited satisfactory nematicidal activity against Meloidogyne incognita at 2-fold dilutions (approximately 3 × 1012 CFU mL-1 ) after 12 h of exposure. Based on their physiological, biochemical and molecular (16S rRNA and gyrB gene sequences) characteristics, the eight strains were identified as Bacillus halotolerans, B. kochii, B. oceanisediminis, B. pumilus, B. toyonensis, B. cereus, Pseudomonas aeruginosa and B. pseudomycoides. In greenhouse and field experiments, the eight isolates suppressed M. incognita up to 69.96% compared to the control. Additionally, the yield of tomato increased 1.4-26.1% over that of the control. CONCLUSION: The strains of B. halotolerans DDWA, B. kochii DDWB, B. oceanisediminis DDWC and B. pseudomycoides JNC have potential to control M. incognita, which has not been previously reported. © 2020 Society of Chemical Industry.


Asunto(s)
Solanum lycopersicum , Tylenchoidea , Animales , Bacterias , Enfermedades de las Plantas , ARN Ribosómico 16S , Suelo , Microbiología del Suelo
19.
Mol Immunol ; 118: 19-29, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31837507

RESUMEN

The role of naturally occurring regulatory T cells (Treg) in the control of the immune tolerance of ANCA-associated vasculitis (AAV) has not been well defined. Therefore, we separate the phenotypically heterogeneous Treg cells into different subsets based on the expression of FOXP3 and CD45RA during AAV pathogenesis. Fifty-four AAV patients (38 patients with renal involvement) and 19 healthy controls (HCs) were enrolled in this study. Levels of CD4+T cell subsets and cytokines were detected by flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The diagnostic value for Treg subsets was evaluated by the areas under the receiver operating characteristic curves (AUC). Patients with AAV had lower percentages and numbers of activated Treg cells (aTreg, P = 0.044, P = 0.002), while higher levels of total Treg cells (P = 0.001, P = 0.026) with diminished immunosuppression capacity. The proportions of effector memory T-cell subpopulation (P < 0.001) were increased in AAV patients. Interestingly, the AUC of the aTreg improved significantly the diagnostic potential of AAV. Furthermore, the ratio of Th17/aTreg was significantly increased in active and renal vasculitis patient and positive correlation between Th17/Treg subset ratio and creatinine or BUN. In addition, we found that cytokine IL-2 and IL-4 exhibited a downward while IL-6, IL-10, TNF-α, IFN-γ and IL-17A trend upward in AAV patients. Increase in total Treg levels, along with functional deficiency, and decrease in aTreg cells constitute potential novel biomarkers for AAV. And the ratio of Th17/aTreg might serve as an important tool to recognize and monitor AAV patients with renal involvement and disease remission.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Vasculitis/inmunología , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Citocinas/inmunología , Femenino , Humanos , Tolerancia Inmunológica/inmunología , Memoria Inmunológica/inmunología , Riñón/inmunología , Masculino , Persona de Mediana Edad
20.
Can Respir J ; 2019: 7262065, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31885749

RESUMEN

Objective: The absolute and relative changes of peripheral NK and T subsets are unclear in rheumatoid arthritis (RA) associated with pulmonary interstitial fibrosis (RA-ILD). To investigate the clinical risk factors, especially the changes of lymphocyte subsets, in RA-ILD in order to make early diagnosis and achieve prevention of the pulmonary interstitial lesions. Methods: A total of 100 RA and 100 RA-ILD patients were enrolled. Rheumatoid factor, anti-cyclic citrulline peptide antibody, erythrocyte sedimentation rate, immunoglobulin, and C-reactive protein were examined. The percentage and absolute number of NK, T, B, Treg, Th1, Th2, and Th17 cells in peripheral blood were determined by flow cytometry. Results: RA-ILD is more common in older and male RA patients and/or those with higher autoantibody titers. Flow cytometry showed that the absolute and relative numbers of CD56+ NK cells were significantly higher in RA-ILD (280.40 ± 180.51 cells/µl vs. 207.66 ± 148.57 cells/µl; 16.62 ± 8.56% vs. 12.11 ± 6.47%), whereas the proportion of T cells and CD4+ T cells was lower in peripheral blood of RA-ILD patients (69.82 ± 9.30%; 39.44 ± 9.87 cells/µl) than that in RA patients (74.45 ± 8.72%; 43.29 ± 9.10 cells/µl). Conclusions: The occurrence of RA-ILD is closely related to the older male patients with high titer of various self-antibodies. Imbalance of CD3-CD56+ NK cells and T cells with other subsets were found in RA-ILD patients, which, together with older age, male, and high levels of autoantibodies should be considered as risk factors of pulmonary interstitial lesions.


Asunto(s)
Anticuerpos Antiproteína Citrulinada/inmunología , Artritis Reumatoide/inmunología , Células Asesinas Naturales/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Fibrosis Pulmonar/inmunología , Factor Reumatoide/inmunología , Linfocitos T/inmunología , Adulto , Factores de Edad , Anciano , Artritis Reumatoide/complicaciones , Linfocitos B/inmunología , Sedimentación Sanguínea , Proteína C-Reactiva/inmunología , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Enfermedades Pulmonares Intersticiales/complicaciones , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Fibrosis Pulmonar/complicaciones , Factores Sexuales , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunología
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