ABSTRACT
Irritable Bowel Syndrome (IBS) is a complex functional gastrointestinal disorder primarily characterized by chronic abdominal pain, bloating, and altered bowel habits. Chronic abdominal pain caused by visceral Hypersensitivity (VH) is the main reason why patients with IBS seek medication. Significant research effort has been devoted to the efficacy of acupuncture as a non-drug alternative therapy for visceral-hyperalgesia-induced IBS. Herein, we examined the central and peripheral analgesic mechanisms of acupuncture in IBS treatment. Acupuncture can improve inflammation and relieve pain by reducing 5-hydroxytryptamine and 5-HT3A receptor expression and increasing 5-HT4 receptor expression in peripheral intestinal sensory endings. Moreover, acupuncture can also activate the transient receptor potential vanillin 1 channel, block the activity of intestinal glial cells, and reduce the secretion of local pain-related neurotransmitters, thereby weakening peripheral sensitization. Moreover, by inhibiting the activation of N-methyl-D-aspartate receptor ion channels in the dorsal horn of the spinal cord and anterior cingulate cortex or releasing opioids, acupuncture can block excessive stimulation of abnormal pain signals in the brain and spinal cord. It can also stimulate glial cells (through the P2X7 and prokinetic protein pathways) to block VH pain perception and cognition. Furthermore, acupuncture can regulate the emotional components of IBS by targeting hypothalamic-pituitary-adrenal axis-related hormones and neurotransmitters via relevant brain nuclei, hence improving the IBS-induced VH response. These findings provide a scientific basis for acupuncture as an effective clinical adjuvant therapy for IBS pain.
ABSTRACT
OBJECTIVE: The objective of this study is to study the critical role of CENPF in regulation of rheumatoid arthritis with acupuncture treatment. METHODS: PCA was used to analyze the different expression genes between AP treatment group and control group. Volcano plot and random forest model were used to analyze the decreased and increased expression genes. RT-qPCR and IF were used to measure the expression of CENPF in CIA model rat with or without AP treatment. The expression of MCP-1, TNF-α and IL-6 was measured by western blotting. The pathology character and arthritis index were used to analyze the severity of joint injury. RESULTS: PCA data showed that the expression of genes was different between AP treatment group and control group from GEO datasets. Volcano plot and random forest model analysis indicated that CENPF is the most significantly increased expression gene after AP treatment. RT-qPCR and IF assay showed that CENPF is reduced expression in CIA model rat, while CENPF is upregulated expression in CIA model rat with AP treatment. Furthermore, overexpression of CENPF reduced the increasing of MCP-1, TNF-α and IL-6 in CIA model rat. On the contrary, CENPF deficiency induced the expression of MCP-1, TNF-α and IL-6 in CIA model rat. Additionally, the expression of MCP-1, TNF-α and IL-6 in CIA model rat was suppressed, whereas knockdown of CENPF antagonized the decrease of MCP-1, TNF-α and IL-6 in CIA model rat with AP treatment. CONCLUSIONS: CENPF may be a key gene in regulation of the therapeutic effects of acupuncture in rheumatoid arthritis. Rheumatoid arthritis is a globally common autoimmune inflammatory disease found especially in China. Acupuncture (AP), a traditional Chinese medicine (TCM) treatment method, is commonly used for treating rheumatoid arthritis. Many studies have demonstrated that acupuncture alone or in combination with other treatments is beneficial to treat clinical situation of rheumatoid arthritis, thus improving function and quality of life. In this study, we found that centromere protein F (CENPF) is a key gene in rheumatoid arthritis with acupuncture treatment by using differentially expressed genes (DEGs) and random forest model analysis of GSE57983 and GSE77298. Acupuncture helps to up-regulate the expression of CENPF in tissues in rheumatoid arthritis. Functionally, overexpression of CENPF inhibits monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and Interleukin (IL)-6 expressions whereas deficiency of CENPF facilitates MCP-1, TNF-α, and IL-6 expressions in a collagen-induced arthritis (CIA) rat model. Furthermore, knocked down CENPF with acupuncture treatment antagonizes the inhibition of MCP-1, TNF-α, and IL-6 expressions in a CIA rat model. CENPF could be a crucial biomarker in regulating function of acupuncture in treating rheumatoid arthritis.