Acupuncture Relieves Cervical Spondylosis Radiculopathy by Regulating Spinal Microglia Activation Through MAPK Signaling Pathway in Rats.

Purpose: Local acupuncture has been found to have a good analgesic effect in rats with cervical spondylosis radiculopathy (CSR), but it lacks a regulatory effect on traditional Chinese medicine syndrome types of CSR. We proposed "Invigorating Qi and activating Blood" (IQAB) acupuncture, compared with Fenbid, and local electroacupuncture (LEA), to observe whether it has advantages in the protection of the CSR rat model and to elucidate its mechanism through the MAPK (mitogen-activated protein kinase) signaling pathway. Materials and Methods: Male Sprague-Dawley rats were randomly divided into six groups: control, sham, model, Fenbid, LEA, and IQAB. The CSR model was induced by inserting nylon sutures to compress the C4-T1 nerve root. The Fenbid group was treated with ibuprofen sustained-release capsules (15 mg/kg·d, ig). The LEA group received electroacupuncture at both C5 and C7 EX-B2 once a day. The IQAB group received acupuncture at both ST36 and BL17 based on the LEA group's intervention. Mechanical allodynia and gait, morphological changes in the spinal cord, IL-6 and TNF-α levels, MAPKs phosphorylation ratio, monocyte chemoattractant protein-1 (MCP-1) levels in the spinal cord, and the expression of p-p38 in the spinal cord and its colocalization with neurons and glial cell activation markers were detected. Results: Mechanical allodynia, gait disorder, edema, reduced Nissl-positive cell numbers, and increased IL-6 and TNF-α levels in the spinal cord were observed in CSR rats. IQAB significantly alleviated these changes, and the effects were generally comparable to those of Fenbid. Meanwhile, the phosphorylation ratios of p38 and extracellular regulated protein kinase (ERK), co-expression of p-p38 with neuron/microglia, and MCP-1 levels in the spinal cord were markedly down-regulated by IQAB compared with those in CSR model rats. Conclusion: IQAB reduced p38-activation-related microglia activation and MCP-1 levels, thus alleviating pathological changes, inflammation levels in the local spinal cord, and pain behavior of CSR.

Alternative splicing analysis showed the splicing factor polypyrimidine tract-binding protein 1 as a potential target in acute myeloid leukemia therapy.

Alternative splicing (AS) is a universal post-transcriptional regulation process in cells, and increasing evidences have validated its crucial role in tumors. We collected AS event, gene expression, and clinical data of 178 AML patients from The Cancer Genome Atlas (TCGA) project. More than 1,000 AS events were found associated with overall survival (OS), and alternate promoter (AP) events were the most significant. The expression of the KIAA0930 transcript was the most significantly different AS event selected from AP events and significantly correlated with the expression of the splicing factor (SF) polypyrimidine tract-binding protein 1 (PTBP1). Then, the roles of PTBP1 on AS of the KIAA0930 and the proliferation of AML cells were confirmed. KIAA0930 variant 1 (KIAA0930-1) was upregulated and variant 2 (KIAA0930-2) downregulated with knockdown PTBP1 expression of AML cells by specific shRNA. A low level of PTBP1 can decrease the proliferation ability of AML cells. In conclusion, the results showed that PTBP1 might be a potential target for AML therapy.

Immune regulation mechanism of vitamin D level and IL-17/IL-17R pathway in Crohn's disease.

Immune regulation mechanism of vitamin D level and interleukin (IL)-17/IL-17 receptor (IL-17R) pathway in Crohn's disease was studied. Of 40 clean mature healthy rats, 10 rats were used as control group based on random number table, the remaining 30 rats to establish Crohn's disease rat models. After successful modeling, 30 rats were divided into model group, low-dose group and high-dose group with random number table. On the 1st day after modeling, rats in low-dose group were given a single dose of 1,750 IU of vitamin D, and rats in high-dose group a single dose of 7,500 IU of vitamin D. Changes in the condition of rats after modeling were observed and scored. Enzyme-linked immunosorbent assay was used for detecting IL-12, IL-17 and CXCL11 levels, western blotting for detecting IL-17R level, and flow cytometry for detecting Th1 cell and Th17 cell levels in the lamina propria of colon mucosa. Disease activity index scores were significantly lower in low-dose group and high-dose group of rats than those in model group (P<0.05). Those were significantly lower in high-dose group of rats than those in low-dose group (P<0.05). IL-17 and IL-17R levels were significantly lower in high-dose group of rats than those in low-dose group (P<0.05). Th1 cell level was significantly higher in high-dose group of rats than that in low-dose group (P<0.05), but Th17 cell level was lower than that in low-dose group (P<0.05). IL-12 levels were significantly higher in model group, low-dose group and highdose group of rats than those in control group (P<0.05). CXCL11 levels were significantly lower in model group, low-dose group and high-dose group of rats than those in control group (P<0.05). Vitamin D can effectively treat Crohn's disease, which may improve the chemotaxis and differentiation of Th1 cells by inhibiting IL-17/IL-17R pathway, thereby improving immune function and reducing the severity of disease.