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INTRODUCTION: Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. METHODS: In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups-low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)-using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1ß, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. RESULTS: At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1ß significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1ß among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1ß exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. CONCLUSION: IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.
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The expression of nitric oxide synthase 1 (NOS1) and adenosine triphosphate-binding cassette sub-family G member 2 (ABCG2) in cervical cancer tissues was investigated. The messenger ribonucleic acid (mRNA) levels of NOS1 and ABCG2 in 40 cervical cancer specimens and 20 normal cervical specimens were detected via reverse transcription-polymerase chain reaction, and the correlation between them was analyzed via Pearsons correlation analysis. The protein expression levels were detected via western blotting. Moreover, the regulatory mode between NOS1 and ABCG2 and the effects on proliferation and apoptosis of cervical cancer cells were analyzed using the lentiviral transfection technique. The mRNA levels of NOS1 and ABCG2 in the cervical cancer group were significantly increased compared with those in the normal cervical control group (P<0.05). There was a positive correlation between NOS1 and ABCG2 mRNA expression levels in cervical cancer tissues (r=1.246, P=0.014). HeLa and C-33A cell lines with relatively high expression levels of NOS1 and ABCG2 were selected for the in vitro study. After interference in the NOS1 expression in HeLa and C-33A cells with sh-NOS1, the protein expression of ABCG2 was also decreased. However, the protein expression level of NOS1 remained unchanged after interference in the ABCG2 expression (P<0.05). After interference in the NOS1 expression, the proliferation capacities of HeLa and C-33A cells were significantly decreased, but the apoptosis levels were obviously increased (P<0.05). The mRNA expression of NOS1 and ABCG2 in cervical cancer tissues is significantly increased. NOS1, as an upstream signal regulator of ABCG2, regulates the growth and apoptosis of tumor cells. Both NOS1 and ABCG2 are important proliferation-promoting oncogenes in cervical cancer, which are expected to provide a certain theoretical basis for the treatment of cervical cancer.