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1.
Immunol Res ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581614

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease with a risk associated with hormonal and reproductive factors. However, the potential causal effects between these factors and SLE remain unclear. A two-sample Mendelian randomization study was conducted using the published summary data from the genome-wide association study database. Five independent genetic variants associated with hormonal and reproductive factors were selected as instrumental variables: age at menarche, age at natural menopause, estradiol, testosterone, and follistatin. To estimate the causal relationship between these exposure factors and disease outcome, we employed the inverse-variance weighted, weighted median, and MR-Egger methods. In addition, we carried out multiple sensitivity analyses to validate model assumptions. Inverse variance weighted showed that there was a causal association between circulating follistatin and SLE risk (OR = 1.38, 95% CI 1.03 to 1.86, P = 0.033). However, no evidence was found that correlation between AAM (OR = 1.04, 95% CI 0.77 to 1.40, P = 0.798), ANM (OR = 0.99, 95% CI 0.92 to 1.06, P = 0.721), E2 (OR = 1.40, 95% CI 0.14 to 13.56, P = 0.772), T (OR = 1.25, 95% CI 0.70 to 2.28, P = 0.459), and SLE risk. Our study revealed that elevated circulating follistatin associates with an increased risk of SLE. This finding suggests that the regulatory signals mediated by circulating follistatin may provide a potential mechanism relevant to the treatment of SLE.

2.
Inflammopharmacology ; 31(4): 1839-1848, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37148383

RESUMO

BACKGROUND: Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational research was not able to address problems with residual confusion and reverse causality. METHODS: We summarized and retrieved 28 inflammatory cytokines associated with RA, depression, or RA with depression through a literature search. The summary statistics from genome-wide association studies for RA, inflammatory biomarkers, broad depression, and major depression disease phenotypes were used. Mendelian randomization was performed to assess the causal association between RA and inflammatory biomarkers, as well as the effects of inflammatory biomarkers on depression. Bonferroni correction was used to reduce the possibility of false positive results. RESULTS: The study found that evidence for associations of genetically predicted RA was associated with higher levels of interleukin (IL)-9 (OR = 1.035, 95%CI = 1.002-1.068, P = 0.027), IL-12 (OR = 1.045, 95%CI = 1.045-1.014, P = 0.004), IL-13 (OR = 1.060, 95%CI = 1.028-1.092, P = 0.0001), IL-20 (OR = 1.037, 95%CI = 1.001-1.074, P = 0.047), and IL-27 (OR = 1.017, 95%CI = 1.003-1.032, P = 0.021). The level of IL-7 (OR = 1.029, 95%CI = 1.018-1.436, P = 0.030) was significantly related to RA. Only the analysis results between RA and IL-13 were satisfied with the statistical significance threshold corrected by Bonferroni (P < 0.002). However, a causal effect was not found between inflammatory biomarkers and depression. CONCLUSIONS: In the current study the inflammatory cytokines associated with RA comorbid depression may not be the mediators that directly lead to the co-pathogenesis of RA and depression.


Assuntos
Artrite Reumatoide , Estudo de Associação Genômica Ampla , Humanos , Depressão/genética , Interleucina-13 , Análise da Randomização Mendeliana/métodos , Artrite Reumatoide/genética , Biomarcadores , Citocinas/genética , Polimorfismo de Nucleotídeo Único
3.
J Clin Med ; 12(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36769592

RESUMO

A correlation between mental illness and systemic rheumatoid arthritis (RA) has been observed in several prior investigations. However, little is known about the causative relationship between them. The present study aimed to systematically investigate the potential association between genetically determined mental illness and RA. Two-sample bidirectional Mendelian randomization (MR) analysis was performed using publicly released genome-wide association studies (GWAS). We selected independent genetic variants associated with four mental illnesses (bipolar disorder, broad depression, major depression, and anxiety) as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between mental illness and RA. Results of the IVW analysis suggested that genetic predisposition to bipolar disorder was associated with a decreased risk of RA (odds ratio [OR] = 0.825, 95% CI = 0.716 to 0.95, p = 0.007). Furthermore, we did not find a significant causal effect of RA on bipolar disorder in the reverse MR analysis (p > 0.05). In addition, our study found no evidence of a bidirectional causal relationship between genetically predicted broad depression, major depression, anxiety, and RA (p > 0.05). The genetically proxied bipolar disorder population has a lower RA risk, which may indicate that there is a hidden mechanism for inhibiting the pathogenesis of RA in bipolar disorder. However, results do not support a causal connection between depression, anxiety, and RA.

4.
Brain Res ; 1805: 148270, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36773926

RESUMO

Prednisone acetate (PA) has many adverse side effects despite the fact that oral administration of PA is widely administrated in the clinic. However, it is unknown whether PA can cause hippocampal long-term potentiation (LTP) impairment. Therefore, in our study, PA (5 mg/kg·d) through intragastric administration (gavage) was applied to establish a model of impaired hippocampal LTP in C57BL/6 mice, and the method was evaluated by comparing with another method to establish LTP impairment through subcutaneous injection of corticosterone (CORT, 50 mg/kg·d). First, our results showed PA caused a more significant decrease in population spike (PS, %) after high-frequency stimulation (HFS) than CORT, demonstrating PA induced impairment of hippocampal LTP more successfully than CORT. Second, PA caused poorer performance of memory than CORT. Third, PA caused more serious lesions and loss of the granule cell in the dentate gyrus than CORT. Finally, PA caused lower levels of glutamic acid (Glu), N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric acid (GABA) than CORT. All in all, PA (5 mg/kg·d) through intragastric administration (gavage) induced LTP impairment in the hippocampus more successfully than CORT. The neuronal lesions in the dentate gyrus and the consequent decrease of Glu and NMDARs (especially NMDAR2A) may be the cause of LTP impairment.


Assuntos
Hipocampo , Potenciação de Longa Duração , Camundongos , Animais , Prednisona/farmacologia , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Acetatos/farmacologia , Estimulação Elétrica
5.
Lupus ; 32(4): 500-507, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36748829

RESUMO

OBJECTIVE: To accelerate the onset of systemic lupus erythematosus in C57BL/6 mice by injecting cadmium chloride nanoemulsion and shorten the traditional modeling time. METHODS: Pristane cadmium chloride nanoemulsion was prepared, and 66 C57BL/6 mice were randomly divided into four groups. The pristane group was intraperitoneally injected with 0.6 mL of pristane blank nanoemulsion, the model group was injected with 0.6 mL of pristane cadmium chloride nanoemulsion, the Cadmium chloride control group was injected with 0.6 mL of cadmium chloride nanoemulsion, and the control group was injected with the same amount of 0.9% sodium chloride solution. Urine protein content, anti-dsDNA antibody content, Th1 cell/Th2 cell ratio, and kidney staining were detected in each group. RESULTS: The model group began to develop disease in the 4th week, the anti-dsDNA antibody level reached 566.71 ± 1.44 ng/L, and the proteinuria reached 245.38 ± 30.54 ng/mL. The model group showed an onset at least 5 weeks earlier than that in the pristane group. There was no significant difference in anti-dsDNA antibody content between Cadmium chloride control group and blank group. At the 12th week, the Th1/Th2 cell ratio in the model group significantly decreased, and the pathological changes in the kidneys were consistent with the typical manifestations of lupus in mouse models. CONCLUSION: These results suggest that cadmium chloride promotes earlier onset of pristane-induced systemic lupus erythematosus in a C57BL/6 mouse model.


Assuntos
Lúpus Eritematoso Sistêmico , Camundongos , Animais , Cloreto de Cádmio/toxicidade , Camundongos Endogâmicos C57BL , Terpenos/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
6.
Clin Exp Immunol ; 211(2): 184-191, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36539326

RESUMO

Systemic lupus erythematosus (SLE) is a chronic, devastating autoimmune disorder associated with severe organ damage. The roles of Toll-like receptor 9 (TLR9) and NETosis in SLE have been described, suggesting the involvement of NETosis signaling in the development of SLE. Shaoyao-Gancao Decoction (SGT) is a potential medication for the treatment of SLE; however, its potential therapeutic mechanism remains unexplored. To determine the function of SGT in SLE, we treated MRL/lpr female mice with SGT, the main components of which were paeoniflorin (56.949 µg·mL-1) and glycyrrhizin (459.393 µg·mL-1). We found that SGT treatment relieved lymphadenectasis and splenomegaly, reduced urine protein and anti-dsDNA antibody concentrations, and relieved kidney pathology in MRL/lpr mice. SGT could also effectively regulate the oxidation/antioxidant balance, significantly reduce malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in MRL/lpr mice. The neutrophil extracellular trap (NET) content of MRL/lpr mice also decreased to a certain extent after SGT treatment. All these results suggested that SGT might improve the inflammatory damage to tissues caused by oxygen free radicals, thereby regulating the NETosis process mediated by TLR9 and exerting a good therapeutic effect on SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Receptor Toll-Like 9 , Animais , Camundongos , Feminino , Camundongos Endogâmicos MRL lpr , Rim/patologia
7.
Front Genet ; 13: 976579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330450

RESUMO

Objectives: Rheumatoid Arthritis (RA) has been associated with Celiac Disease (CD) in previous observational epidemiological studies. However, evidence for this association is limited and inconsistent, and it remains uncertain whether the association is causal or due to confounding or reverse causality. This study aimed to assess the bidirectional causal relationship between RA and CD. Methods: In this two-sample Mendelian randomization (MR) study, instrumental variables (IVs) for RA were derived from a genome-wide association studies (GWAS) meta-analysis including 58,284 subjects. Summary statistics for CD originated from a GWAS meta-analysis with 15,283 subjects. The inverse-variance weighted (IVW) method was used as the primary analysis. Four complementary methods were applied, including the weighted-median, weighted mode, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression, to strengthen the effect estimates. Results: Positive causal effects of genetically increased RA risk on CD were derived [IVW odds ratio (OR): 1.46, 95% confidence interval (CI): 1.19-1.79, p = 3.21E-04]. The results of reverse MR analysis demonstrated no significant causal effect of CD on RA (IVW OR: 1.05, 95% CI: 0.91-1.21, p = 0.499). According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. Conclusion: This study reveals a causality of RA on CD but not CD on RA among patients of European descent. This outcome suggests that the features and indicators of CD should regularly be assessed for RA patients.

8.
Front Pharmacol ; 13: 988512, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249802

RESUMO

Objective: Th1 and Th2 cells and their associated cytokines function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact roles are uncertain. We performed a meta-analysis to examine the relationship of these cells and cytokines with SLE. Methods: Multiple databases were searched to identify publications that reported the percentages of Th1 and Th2 cells and their associated cytokines in SLE patients and healthy controls (HCs). Meta-analysis was performed using Stata MP version 16. Results: SLE patients had a lower percentage of Th1 cells, a higher percentage of Th2 cells, and higher levels of Th1- and Th2-associated cytokines than HCs. SLE treatments normalized some but not all of these indicators. For studies in which the proportion of females was less than 94%, the percentage of Th2 cells and the level of IL-10 were higher in patients than HCs. SLE patients who had abnormal kidney function and were younger than 30 years old had a higher proportion of Th1 cells than HCs. SLE patients more than 30 years old had a higher level of IL-6 than HCs. Conclusion: Medications appeared to restore the balance of Th1 cells and other disease indicators in patients with SLE. Gender and age affected the levels of Th1 and Th2 cells, and the abnormally elevated levels of Th2 cells appear to be more pronounced in older patients and males. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296540].

9.
Clin Rheumatol ; 41(9): 2647-2658, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35643813

RESUMO

BACKGROUND: The correlation between dietary inflammation index (DII) and rheumatoid arthritis (RA) has been found, but the effect of confounding factors is not considered. This study aims to further explore the association between DII and RA risk by taking the Americans as the research object. METHODS: The data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) database included 1819 self-reported RA individuals and 8602 non-RA individuals. The analytical methods include logistic regression, additive model, smooth curve fitting, and the recursive algorithm. RESULTS: There was a positive correlation between DII and RA in Americans (ß = 1.068, 95% CI = 1.026 to 1.111, P = 0.001). This result was still presented in the subgroup analysis, including age less than 50 years, female, other Hispanics, BMI ≥ 25, and federal poverty rate > 185%, and it was more pronounced in smokers. The results show that the superposition of DII and other risk factors would increase the risk of RA (ß > 1.068). In addition, individuals with RA are inadequate in intake of anti-inflammatory foods, in line with the Mediterranean diet. CONCLUSIONS: The inflammatory potential of the diet is positively correlated with the risk of RA, and has a superimposed effect with other risk factors, increasing the probability of the risk of disease. These results emphasize that reducing the intake of pro-inflammatory foods may be an effective measure to prevent the onset of rheumatoid arthritis. However, eating anti-inflammatory foods exclusively is not the best option. Intaking some pro-inflammatory foods like protein, energy, and total saturated acids may be necessary to maintain the physiological function of the human body. Key Points • Dietary inflammation index (DII) is positively correlated with RA risk. • When DII and other risk factors appear at the same time, the effects of the two will be superimposed on each other, increasing the risk of RA. • When the DII is the same, Hispanic has a higher incidence of RA. • Among the pro-inflammatory foods, the intake of protein, energy, and saturated fatty acids is still required by RA patients.


Assuntos
Artrite Reumatoide , Dieta Mediterrânea , Artrite Reumatoide/epidemiologia , Dieta/efeitos adversos , Feminino , Humanos , Inflamação/diagnóstico , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de Risco
10.
Lupus Sci Med ; 9(1)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35346981

RESUMO

OBJECTIVE: Recent studies reported that SLE is characterised by altered interactions between the microbiome and immune system. We performed a meta-analysis of publications on this topic. METHODS: Case-control studies that compared patients with SLE and healthy controls (HCs) and determined the diversity of the gut microbiota and the abundance of different microbes were examined. Stata/MP V.16 was used for the meta-analysis. A Bonferroni correction for multiple tests was used to reduce the likelihood of false-positive results. RESULTS: We included 11 case-control studies that examined 373 patients with SLE and 1288 HCs. These studies were performed in five countries and nine cities. Compared with HCs, patients with SLE had gut microbiota with lower Shannon-Wiener diversity index (weighted mean difference=-0.22, 95% CI -0.32 to -0.13, p<0.001) and lower Chao1 richness (standardised mean difference (SMD)=-0.62, 95% CI -1.04 to -0.21, p=0.003). Patients with SLE had lower abundance of Ruminococcaceae (SMD = -0.49, 95% CI -0.84 to -0.15,p=0.005), but greater abundance of Enterobacteriaceae (SMD=0.45, 95% CI 0.01 to 0.89, p=0.045) and Enterococcaceae (SMD=0.53, 95% CI 0.05 to 1.01, p=0.03). However, only the results for Ruminococcaceae passed the Bonferroni correction (p=0.0071). The two groups had no significant differences in Lachnospiraceae and Bacteroides (both p>0.05). Patients with SLE who used high doses of glucocorticoids had altered gut microbiota based on the Chao1 species diversity estimator, and hydroxychloroquine use appeared to reduce the abundance of Enterobacteriaceae. CONCLUSIONS: Patients with SLE have imbalanced gut microbiota, with a decrease in beneficial bacteria and an increase in harmful bacteria. Drugs used to treat SLE may also alter the gut microbiota of these patients.


Assuntos
Microbioma Gastrointestinal , Lúpus Eritematoso Sistêmico , Estudos de Casos e Controles , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico
11.
BMC Musculoskelet Disord ; 22(1): 300, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757488

RESUMO

INTRODUCTION: The appropriate and optimal treatment for thoracic and lumbar (TL) burst fractures remains a topic of debate. Characterization of vertical laminar fractures (coronal cross-sectional imaging) is presented in this study to determine the severity and treatment options in TL burst fractures. METHODS: A retrospective evaluation of 341 consecutive patients with TL burst fractures was divided into Group I (whole), Group II (partial), and Group III (intact) based on the vertical laminar fracture morphology from coronal images on computed tomography (CT) scans. The presence of preoperative neurological status was reviewed, and several radiological parameters were measured. In addition, the incidence of dural tears was calculated in patients that underwent a decompression with posterior approach. RESULTS: In total, 270 lumbar and 71 thoracic burst fractures were analyzed. Compared with the intact group, the two other groups had significantly shorter central canal distance, wider interpedicular distance, and smaller spinal canal area, in particular, Group III. The incidences of preoperative neurological deficits in Groups I to III were 63.0, 22.2, and 6.3%, respectively. The incidences of dural tears in Groups I to III were 25.6, 6.3, and 0%, respectively. CONCLUSION: The morphology of vertical laminar fractures observed across the coronal plane was important. Patients with "whole", "partial" and "intact" laminar fractures indicated different severity of TL burst fractures. Due to the high probability of dural tears, decompression is recommended as a primary intervention for patients with "whole" laminar fractures. However, for patients without vertical laminar fractures, minimally invasive technique might be a better choice to avoid approach-related complications.


Assuntos
Fraturas por Compressão , Fraturas da Coluna Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia
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