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ObjectiveTo investigate the possible mechanism of Fugan Huaxian Decoction （扶肝化纤汤， FHD） against hepatic fibrosis （HF） from the perspective of immunity. MethodsForty-eight SD rats were randomly divided into blank group， model group， colchicine group， FHD high-， medium- and low-dose group， with eight rats in each group. Except for the blank group， the disease-syndrome combined model of HF with healthy qi deficiency and toxin accumulation pattern was established during six weeks in the other five groups. After successful modeling， the high-， medium- and low-dose FHD groups were respectively given 37.5， 18.75 and 9.38 g/（kg·d） of FHD granules by gavage， while the colchicine group received 2 mg/ （kg·d） of colchicine tablets by gavage， and the blank group and the model group were given 10 ml/（kg·d） of purified water， all for 3 weeks. The general condition of the rats was recorded. After the treatment， the histopathological morphology of the liver was observed by HE staining， and the levels of interleukin 10 （IL-10） and interleukin 17 （IL-17） in serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of helper T cells 17 （Th17） and regulatory T cells （Treg） in peripheral blood were detected by flow cytometry， and the Th17/Treg value was calculated. The mRNA expression of retinoic acid-related nuclear orphan receptor γ （RORγt） and fork-head/wing-like helix transcription factor （FoxP3） in liver tissue were detected by qRT-PCR. ResultsCompared to the general condition of rats in the blank group， those in the model group were listless， less active， stretched and pushed， arched and prone， having no resistance to gavage， significantly reduced food intake， loose stools， dirty anus， slow weight gain， dry and dull hair， purple and darkening skin of the limbs with ecchymoses， purple and black spots with varying degrees of the skin of the tail； hepatic fibrosis and hyperplasia of rats in model group were more obvious； serum IL-17， peripheral blood Th17 expression and Th17/Treg value， RORγt mRNA expression in the liver tissue significantly increased in the model group， while expression of IL-10， Treg and FoxP3 mRNA significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the general condition of the rats and the liver fibrosis of HE stained liver tissue were improved in all the medication groups； the expression of IL-17 and Th17， Th17/Treg， and RORγt mRNA expression significantly decreased， while expression of IL-10， Treg， and FoxP3 mRNA increased in the high- and medium-dose FHD groups and the colchicine group； the expression of IL-17， Th17， and RORγt mRNA decreased， while the expression of IL-10 and FoxP3 mRNA increased in the low-dose FHD group （P＜0.05 or P＜0.01）. And more improvements were found in the FHD high-dose group than FHD medium- and low-dose groups and colchicine group （P＜0.05 or P＜0.01）. ConclusionFHD can may regulate immune balance and act against fibrosis by regulating the expression of specific transcription factors FoxP3 and RORγt， affecting the differentiation of Th17 and Treg cells and Th17/Treg balance， and regulating the secretion of IL-10 and IL-17.
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Objective To investigate the diagnostic value of Bcl-2, miR-451 and Th17 cells in esophageal cancer and their relation with recurrence. Methods We selected 101 patients with esophageal cancer as the experimental group and 95 healthy patients as the control group. The correlation between the clinicopathological characteristics and the level of each peripheral blood index was analyzed. The ROC curve was used to analyze the diagnostic value of each peripheral blood index. Multiple linear regression analysis was used to analyze the relation between each index and tumor recurrence. Results Peripheral blood Bcl-2, miR-451 and Th17 cells in the experimental group were higher than those in the control group (all P < 0.05); differentiation degree, clinical stage, tumor diameter and lymph node metastasis were positively correlated with the levels of Bcl-2, miR-451, and Th17 cells (all P < 0.05). Bcl-2, miR-451 and Th17 cells in relapsed patients were higher than those in non-relapsed patients (all P < 0.05); after controlling other factors such as differentiation degree, clinical stage, tumor size and lymph node metastasis, the levels of Bcl-2, miR-451 and Th17 cells were significantly correlated with recurrence (all P < 0.05). Conclusion Bcl-2, miR-451 and Th17 cells in peripheral blood of esophageal cancer patients are abnormally expressed and their expression are closely related to differentiation degree, clinical stage and recurrence. The combined detection could provide an objective basis for clinical diagnosis and prognosis assessment.
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@#T helper 17 (Th17) cells are a new type of CD4+ T helper cell. They participate in the immune and inflammatory response by secreting specific interleukin-17 (IL-17). In oral mucosal diseases, oral lichen planus (OLP), recurrent aphthous ulcer (RAU) and Behcet′s disease (BD) are associated with Th17 cells and IL-17. There were 17 kinds of proteins in the saliva of patients with OLP that could upregulate the expression of Th17 cells and induce the secretion of IL-17. IL-17 can stimulate epithelial cells, endothelial cells and fibroblasts to produce a variety of cytokines, such as IL-6, IL-8, granulocyte macrophage colony-stimulating factor and cell adhesion molecule-1, leading to the production and aggravation of inflammation. Th17/Tc17 cell-targeted therapy can significantly improve the clinical symptoms of OLP patients′ mucosa and skin. IL-17 can stimulate oral keratinocytes through the IL-17RA or IL-17RE receptor and produce proinflammatory effects in RAU. Th17 cells in the peripheral blood of BD patients are significantly increased, while Treg cells are significantly decreased.
ABSTRACT
Under the regulation of various cytokines and different concentrations of cytokines, primary CD4+ T cells can differentiate into different Th subgroups. T helper cells 17 (Th17) and regulatory T cells (Treg cells) are research hotspots in recent years. They play diverse immunomodulatory roles by secreting various target cytokines. Th17 and Treg cells are different from each other but connect with each other, their regulatory mechanism is complex, and they play important roles in non-small cell lung cancer (NSCLC). This paper reviews the progress of the differentiation, the development and the immunological function of Th17 and Treg cells and their immunomodulatory effect on the NSCLC.
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Objective@#To investigate the effect of compound sophora flavescens injection on T helper cells 17 (Th17), regulatory T-cells (Treg cells) and the related cytokines in lung cancer patients with cirrhosis.@*Methods@#A total of 63 patients with early non-small cell lung cancer and cirrhosis in Shouguang People's Hospital of Shandong Province from January 2016 to January 2018 were selected. All patients were scheduled to undergo surgical treatment. The patients were randomly divided into observation group (33 cases) and control group (30 cases) according to the random number table method. The patients in the control group were treated with liver protection, and the patients in the observation group were given compound sophora flavescens on the basis of the control group. After 3 months of treatment, the changes of liver fibrosis index, the levels of Th17 and Treg cells in peripheral blood and the changes of interleukin (IL)-10, IL-17, IL-6, and transforming growth factor (TGF)-β in serum were compared between the two groups.@*Results@#After treatment, the alanine aminotransferase (ALT) of 15 cases (45.45%) in the observation group were normalized and 6 cases (20.00%) in the control group were normalized. There was a significant difference in ALT normalization rate between the two groups (P < 0.05). The levels of serum laminin (LN) and hyaluronic acid (HA) in the two groups after treatment were lower than those before treatment (all P < 0.05), and the serum LN [(156.74±30.52) ng/ml] and HA [(179.56±25.32) ng/ml] in the observation group after treatment was lower than those in the control group [(210.58±39.42) ng/ml and (203.75±28.79) ng/ml] (t values were 18.236 and 12.184, both P < 0.01). There was no significant difference in the level changes of type Ⅲ procollagen and type Ⅳ collagen between the two groups before and after treatment (all P > 0.05). After treatment, the levels of Th17 and Th17/Treg increased and the level of Treg cells decreased (all P < 0.05). After treatment, the levels of Th17 [(1.32±0.18)%] and Th17/Treg (0.23±0.04) in the observation group were higher than those in the control group [(1.21±0.17)% and 0.20±0.03] (t values were 3.201 and 1.087, both P < 0.01), while the level of Treg cells in the observation group was lower than that in the control group (P < 0.05). After treatment, the serum levels of IL-10, IL-17, IL-6, and TGF-β in the two groups were lower than those before treatment (all P < 0.05), and their levels in the observation group were lower than those in the control group (all P < 0.05).@*Conclusion@#Compound sophora flavescens injection can improve the liver function and fibrosis index of patients with lung cancer and cirrhosis, and it can regulate the levels of Th17, Treg cells and their related factors, which can be used as a clinical adjuvant.