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1.
Mol Med ; 30(1): 81, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862942

RESUMO

BACKGROUND: Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases. METHODS: RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways. RESULTS: COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages. CONCLUSIONS: The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity.


Assuntos
COVID-19 , Estudo de Associação Genômica Ampla , Lúpus Eritematoso Sistêmico , SARS-CoV-2 , Transdução de Sinais , Humanos , COVID-19/genética , Lúpus Eritematoso Sistêmico/genética , SARS-CoV-2/fisiologia , Feminino , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/genética , Masculino , Transcriptoma , Perfilação da Expressão Gênica , Multiômica
2.
Int J Gen Med ; 16: 1393-1401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37155468

RESUMO

Purpose: This study aimed to compare the changes in the expression of microRNA Let-7i in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and the correlation between Let-7i and innate pro-inflammatory factors. It is necessary to search for a new biomarker to guide the prognosis of AS. Methods: A total of 10 patients with AS and 10 healthy volunteers were selected as AS and control groups, respectively. The expression levels of Let-7i, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and interferon-gamma (IFN-γ) in PBMCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) to explore the relationship between Let-7i and pro-inflammatory factors. Furthermore, the relationship between Let-7i and TLR4 was determined by the luciferase reporter technology. Results: The expression level of Let-7i in PBMCs of patients with AS was significantly lower than that of healthy control. The expression levels of TLR4, NF-κB, and IFN-γ in PBMCs derived from patients with AS were significantly higher than those of healthy control. The results show that Let-7i manipulation can regulate lipopolysaccharide (LPS)-induced TLR4 and IFN-γ expression in CD4+ T cells of patients with AS. The overexpression of Let-7i in T cells of patients with AS can suppress TLR4 and IFN-γ LPS-induced expression levels of cellular mRNA and protein. Let-7i can directly interfere TLR4-3'untranslated region (UTR) sequence and regulate the expression of the TLR4 gene in Jurkat T cells. Conclusion: Let-7i may be involved in the pathogenesis of AS, and Let-7i expression in PBMCs may be helpful for the diagnosis and treatment of AS in the future.

3.
Epigenomics ; 12(11): 973-988, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32677847

RESUMO

Aim: We aimed to identify differentially expressed Long noncoding RNAs (lncRNAs) and explore their functional roles in systemic lupus erythematosus (SLE). Materials & methods: We identified dysregulated lncRNAs and investigated their prognostic values and potential functions using MiRTarget2, catRAPID omics and Bedtools/blast/Pearson analyses. Results: Among the 143 differentially expressed lncRNAs, TCONS_00483150 could be used to distinguish patients with SLE from healthy controls and those with rheumatoid arthritis and patients with active/stable SLE from healthy controls. TCONS_00483150 was significantly correlated with anti-Rib-P antibody positivity and low C3 levels; TCONS_00483150 dysregulation might contribute to the metabolism of RNA and proteins in SLE patients. Conclusion: Overall, our findings offer a transcriptome-wide overview of aberrantly expressed lncRNAs in patients with SLE and highlight TCONS_00483150 as a potential novel diagnostic biomarker.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , RNA Longo não Codificante , Artrite Reumatoide , Biomarcadores , Estudos de Casos e Controles , Humanos , Lúpus Eritematoso Sistêmico/genética , RNA Longo não Codificante/genética , Transcriptoma
4.
Connect Tissue Res ; 53(5): 355-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22288847

RESUMO

The purpose of this study was to investigate the efficacy of intra-articular injection of infliximab in a rabbit model of osteoarthritis. In 30 New Zealand white rabbits, the cruciate ligaments and medial menisci were resected using the Hulth technique. Eight weeks postsurgery, the animals were randomly divided into three groups, and each group was given monthly intra-articular injections (0.5 ml) of 10 mg/ml infliximab, 20 mg/ml infliximab, or saline, respectively. After 3 months, the results were assessed by macroscopic observation, histological evaluation, and measurement of the levels of interleukin-1ß, tumor necrosis factor-α, and nitric oxide in the synovial fluid. In the two groups of rabbits administered infliximab (10 or 20 mg/ml), the pathological changes were more attenuated than in the group administered saline. Mankin scores in the rabbits administered infliximab 10 mg/ml (2.7 ± 0.9) or infliximab 20 mg/ml (2.4 ± 0.7) were significantly lower than in the control group (6.4 ± 1.2) (p <0.05). The tumor necrosis factor-α and nitric oxide contents of the synovial fluid were also decreased significantly in the rabbits administered infliximab at both concentrations compared with the saline-injected rabbits (p <0.05). Administration of infliximab did not change the levels of interleukin-1ß in the synovial fluid. Similar results were obtained for all analyses with the two concentrations of infliximab tested. This study demonstrates that intra-articular injections of infliximab can protect against the development of experimentally induced osteoarthritis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Osteoartrite/tratamento farmacológico , Animais , Anticorpos Monoclonais/farmacologia , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Fêmur/patologia , Infliximab , Interleucina-1beta/metabolismo , Masculino , Óxido Nítrico/metabolismo , Osteoartrite/patologia , Coelhos , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
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