In Rheumatoid Arthritis, A Review of ncRNAs Related to NF-κB Signaling Pathways.

Rheumatoid arthritis (RA) is an autoimmune disease with no known cure that results in joint deformities and dysfunction, significantly impacting the quality of life of patients. The abnormal NF-ＫB signaling pathway in RA has emerged as a crucial research area for the development of RA therapies, with non-coding RNAs (ncRNAs) serving as a potentially meaningful avenue to regulate it. Thus, understanding the role of ncRNAs in RA and the identification of new therapeutic targets have become pressing issues in the field. In this review, we aim to summarize recent studies on ncRNAs that regulate the NF-ＫB signaling pathway in RA, including miRNAs, lncRNAs, and circRNAs, as well as the mechanisms by which drugs modulate NF-Ｋ B activity. By highlighting these recent advances, we hope to promote further research into targeted RA therapy and provide novel directions and ideas for researchers in the field.

Bilobalide protects against ischemia/reperfusion-induced oxidative stress and inflammatory responses via the MAPK/NF-íœ B pathways in rats.

BACKGROUND: Clinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury. METHODS: The effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-휅B pathway members. RESULTS: Bilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-휅B pathways. CONCLUSIONS: Bilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.

Migration and Invasion Enhancer 1 Is an NF-ĸB-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo.

: Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. We determined the expression, biological functions, and regulatory mechanisms of MIEN1 in the prostate. The results of immunohistochemical analysis indicated that MIEN1 was expressed specifically in epithelial cells and significantly higher in adenocarcinoma as compared to in normal tissues. MIEN1 enhanced in vitro cell proliferation, invasion, and in vivo tumorigenesis. Meanwhile, MIEN1 attenuated cisplatin-induced apoptosis in PC-3 cells. Overexpression of NF-ĸB-inducing kinase (NIK) enhanced MIEN1 expression, while overexpression of NF-ĸB inhibitor α (IĸBα) blocked MIEN1 expression in PC-3 cells. In prostate carcinoma cells, MIEN1 provoked Akt phosphorylation; moreover, MIEN1 downregulated N-myc downstream regulated 1 (NDRG1) but upregulated interleukin-6 (IL-6) gene expression. MK2206, an Akt inhibitor, impeded the modulation of MIEN1 on NDRG1 and IL-6 expressions. Our studies suggest that MIEN1 is an NF-ĸB downstream oncogene in the human prostate. Accordingly, the modulation of Akt signaling in the gene expressions of NDRG1 and IL-6 may account for the functions of MIEN1 in cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells.

The Expression of SOCS and NF-Ï°B p65 in Hypopharyngeal Carcinoma.

BACKGROUND: Hypopharyngeal carcinoma is one of the most common types of head and neck tumors. Suppressers of cytokine signalling (SOCS) family members are key regulators of cytokine homeostasis, they play important roles in the process of cell proliferation, differentiation, maturation and apoptosis, and participate in the occurrence and development of tumor. The abnormal activation of NF-Ï°B is an important feature of the tumor. The aim of this study was to investigate the relationships among SOCS, NF-Ï°B p65 and hypopharyngeal carcinoma development.C. METHODS: We included 72 hypopharyngeal cancer patients and 9 swallow cyst patients. The patients were recruited at The Second Hospital of Shandong University (Jinan, China) between 2014 and 2016. The mRNA and protein expression levels of SOCS-1, SOCS-3 and NF-Ï°B p65 in hypopharyngeal carcinoma tissues, para-cancerous tissues and control tissues were detected by RT-PCR and Western blot analysis, respectively. RESULTS: Hypopharyngeal carcinoma tissues had lower level expression of SOCS-1 and SOCS-3 than pericarcinoma tissues, but there was no significant difference, while cancer tissues had significantly higher level expression of NF-Ï°B p65 than that of pericarcinoma tissues (0.412±0.266, 0.281±0.231, t=2.969, P=0.004). The early stage patients had striking higher level expression of SOCS-1 and SOCS-3 than that in advanced stages (F=16.202, P<0.001; F=52.295, P<0.001), while the expression of NF-Ï°B p65 in early stages had lower level than that in advanced stages (F=3.383, P=0.04). CONCLUSION: SOCS-1, SOCS-3 may be protective factors while NF-Ï°B p65 could be a harmful factor in hypopharyngeal carcinoma.

Modulation of nuclear factor-Ï°B by human T cell leukemia virus type 1 tax protein : Implications for oncogenesis and inflammation.

Activation of the nuclear factor kappa B (NF-Ï°B) transcription factor family by different stimuli, such as inflammatory cytokines, stress inducers, or pathogens, results in innate and adaptive immunity. While the main function of NF-Ï°B is to promote the host's immune response, the NF-Ï°B pathway is frequently dysregulated by invading viral pathogens. Human T cell leukemia virus type 1 (HTLV-1) is the causative agent of a fatal malignancy known as adult T cell leukemia (ATL) and an inflammatory disease named tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). HTLV-1 encodes an oncoprotein, Tax, which plays a significant role in the initiation of cellular transformation and the elicitation of the host's inflammatory responses. Here, we review current thinking on how Tax may affect both diseases through activation of NF-Ï°B signaling.