Research progress about traditional Chinese medicine in the intervention of gastric cancer by regulating Th17/Treg balance / 中国药房

Gastric cancer （GC） is a common malignant tumor of the digestive tract. T helper cells 17 （Th17） and T regulatory cells （Treg） are differentiated subsets of CD4+T cells. Th17/Treg imbalance has been shown to be closely related to the progression of GC. Traditional Chinese medicine （TCM） can not only improve the survival prognosis of GC patients， but also play a role in enhancing the efficacy and reducing the toxicity of postoperative chemotherapy for GC. This paper systematically sorted out the action rules of TCM in the intervention of GC by regulating Th17/Treg balance. The results showed that the TCM compound could regulate the balance of GC Th17/Treg by invigorating the spleen and invigorating Qi， warming Yang， removing blood stasis and detoxifying. The mechanism of regulating Th17/Treg balance in the intervention of GC is mainly to inhibit the excessive differentiation of Th17 and Treg and the overexpression of transcription factors and cytokines， reverse the excessive drift of GC Th17/Treg balance to Th17 or Treg， and thus restore the immune balance of GC Th17/Treg.

Comparison on Ameliorating Effect of Arisaematis Rhizoma and Arisaematis Rhizoma Preparatum on Allergic Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg-1） and ARP （1.2， 0.3 g∙kg-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

Expression and Clinical Significance of Helper T Cells 9 and Its Sytokines Interleukin 9 in Chronic Lymphocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL).@*METHODS@#A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed.@*RESULTS@#The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(rs=-0.32，rs=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (rs=0.79，rs=0.54，rs=0.58； rs=0.72，rs=0.63，rs=0.45), but not with WBC, CD4+ T cells and CD8+T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (rs=0.53).@*CONCLUSION@#Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.

Influence of matrine on Th17/Treg balance in rats with inflammatory bowel disease by regulating IL-6/STAT3/NF-κB signaling pathway / 西安交通大学学报(医学版)

【Objective】 To investigate the influence of matrine (MT) on the balance of T helper cell 17 (Th17)/regulatory T cells (Treg) in rats with inflammatory bowel disease by regulating interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3)/nuclear transcription factor-κB (NF-κB) pathway. 【Methods】 SD rats were grouped into control check group (CK group), model group, low-dose MT group (MT-L group, 50 mg/kg), medium-dose MT group (MT-M group, 100 mg/kg), high-dose MT group (MT-H group, 200 mg/kg), mesalazine group (MSLM group, 0.42 g/kg), and MT-H+rIL-6 (IL-6 activator) group (200 mg/kg+0.05 mg/kg) according to the random number table method, with 18 in each group. Except for the CK group, the rats in other groups all received with 5% trinitrobenzenesulfonic acid (20 mg/kg) buffer solution mixed with 50% ethanol at a ratio of 1∶1 and then enema to construct a rat model of inflammatory bowel disease. After the successful modeling, they were treated with drug administration once a day for 7 weeks. The body weight of rats was measured at 1, 3, 5, and 7 weeks of administration; the changes of colon length of rats in each group were compared; HE staining was used to detect the pathological damage of rat colon tissue; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-17 and IL-10 in serum of rats were detected by ELISA; the proportions of Th17 and Treg cells in peripheral blood of rats were detected by flow cytometry; Western blottingt was performed to detect the protein expression of retinoic acid-related orphan receptor γt (RORγt), forkhead box protein P3 (Foxp3), IL-6, p-STAT3, and p-NF-κB p65 in rat colon tissue. 【Results】 Compared with the CK group, the colon tissue of the model group was severely damaged by pathology, and the body weight (at 3, 5, and 7 weeks), the level of IL-10, the proportion of Treg cell, and the expression of Foxp3 protein were decreased, the colon length shortened, the levels of TNF-α, IL-17, the proportions of Th17 cell, Th17/Treg ratio, and the protein expression of RORγt, IL-6, p-STAT3, and p-NF-κB p65 increased (P<0.05). Compared with the model group, the corresponding indicators of the MT-L group, MT-M group, MT-H group, and MSLM group had the opposite trends (P<0.05); rIL-6 attenuated the promoting effect of high-dose MT on Th17/Treg balance in inflammatory bowel disease rats. 【Conclusion】 MT may promote Th17/Treg balance in inflammatory bowel disease rats by inhibiting IL-6/STAT3/NF-κB signaling pathway.

Triptolide regulates the balance of Tfr/Tfh in lupus mice

Abstract Introduction/objectives Systemic lupus erythematosus (SLE) is a classic prototype of the multisystem autoimmune disease and follows a relapsing and remitting course. Triptolide is a diterpene triepoxide extracted from Chinese medicine Tripterygium wilfordii Hook F, with potent immunosuppressive and anti-inflammatory properties. Our previous work observed that triptolide alleviated lupus in MRL/lpr lupus mice with the upregulation of regulatory T cells (Treg) proportion in previous study. In this study, we explored the proportion of follicular T regulatory (Tfr), follicular T helper (Tfh) and germinal center (GC) B cells in lupus mice and evaluated the efficacy of triptolide for lupus treatment in vivo. Methods 20 female MRL/lpr mice were randomly divided into 2 treatment groups and treated orally with vehicle or triptolide. C3H mice were all housed as controlled group and treated orally with vehicle. The percentage of Tfr cells, Tfh cells and GC B cells in spleen of mice were detected by Flow cytometric analysis and immunohistochemistry after 13 weeks of treatment. Results We found that the percentage of Tfr cells decreased in MRL/lpr mice compared with controlled mice. The percentage of Tfh cells in MRL/lpr mice was significantly higher compared with that in controlled mice. The ratio of Tfr/Tfh is also decreased in lupus mice. After treated with triptolide in MRL/Lpr mice in vivo, the percentage of Tfr cells and ratio of Tfr/Tfh increased. The proportion of GC B cells also decreased in mice treated with triptolide by FACS and immunohistochemistry. Conclusions Our results demonstrate that the effect of triptolide in alleviating lupus is partly by reversing immune imbalance with increased percentage of Tfr cells and ratio of Tfr/Tfh. Triptolide might also has effect on immune response through inhibiting proliferating GC B cells.

Effect of crosstalk between Th17 and Th9 cells on the activation of dermal vascular smooth muscle cells in systemic scleroderma and regulation of tanshinone IIA

Abstract Background: To evaluate the effect of T-helper 17 (Th17) cells and Th9 cells on the activation of dermal vascular smooth muscle cells (DVSMCs) in systemic scleroderma (SSc) and regulation of tanshinone IIA. Methods: The expression of interleukin 17 receptor (IL-17R) and interleukin 9 receptor (IL-9R) in the skin of SSc patients was assessed by immunofluorescence. The expression of IL-9 and IL-9R mRNA in peripheral blood mononuclear cells (PBMCs) of SSc patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proportion of Th9 cells in PBMCs of SSc patients was sorted by flow cytometry. The effect of IL-9 on the differentiation of Th17 and IL-17 on that of Th9 was detected by flow cytometry. The proportion of Th9 and Th17 cells in SSc patients was detected by flow cytometry. The level of collagen I, III, α-SMA, IL-9R, IL-17R, JNK, P38, and ERK were analyzed using western blot (WB). Results: Th9 cells were highly expressed in SSc. IL-9 stimulated the differentiation of immature T cells into Th17 cells. IL-17 induced the differentiation of immature T cells intoTh9 cells. Tanshinone IIA inhibited the differentiation of immature T lymphocytes into Th17 and Th9. WB showed that the combined action of IL-17 and IL-9 upregulated the inflammation and proliferation of DVSMCs. Anti-IL17, anti-IL9, and tanshinone IIA inhibited the functional activation of DVSMCs. Study limitations: For Th17, Th9 and vascular smooth muscle cells, the study on the signal pathway of their interaction is not thorough enough. More detailed studies are needed to explore the mechanism of cell-cell interaction. Conclusions: The current results suggested that Th17 and Th9 cells induced the activation of DVSMCs in SSc through crosstalk in vitro, and tanshinone IIA inhibited the process.

Research advance in Hashimoto thyroiditis mediated by T helper cell 17 / 中华内分泌代谢杂志

Hashimoto thyroiditis(HT) is a classic autoimmune thyroiditis (AIT), characterized by diffuse lymphocytic infiltration, destruction of thyroid structure, and positive autoantibodies. The pathogenesis of HT is complex and related to genetic susceptibility, immune system disorders, and environmental factors. The imbalance of T helper cell 1 (Th1)/ T helper cell 2 (Th2) is traditionally believed to be the main mechanism of HT. However, recent studies have shown that T helper cell 17 (Th17) plays an important role in the occurrence and development of HT through non-coding RNA regulation, autophagy-related pathway regulation, the balance with regulatory T cell (Treg). These mechanisms can enhance the release of inflammatory factors and aggravate HT by stimulating the differentiation of Th17, the inflammatory environment of HT also further stimulates the differentiation of Th17 and amplifies the inflammatory response. The regulatory mechanisms of Th17 are complex and have not yet been fully studied. Therefore, this article reviews the related mechanism of Th17 in HT to provide insights for novel therapeutic targets.

Effect of Xiao Qinglongtang on IL-33/ST2 Signaling Pathway in Mice with Allergic Rhinitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa. ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.

The functions of Th17/Treg cells and relevant studies on the treatment of periodontitis and atherosclerosis / 口腔疾病防治

@#Periodontitis is a chronic infectious disease in which periodontal tissue loss is caused by dental plaque biofilm. Atherosclerosis is a chronic inflammatory disease that occurs in the walls of arteries and is characterized by lipid accumulation. Recently, many studies have suggested that there is a certain relationship between periodontitis and atherosclerosis. From an epidemiological perspective, a previous literature review indicated that patients with periodontitis have a higher incidence of atherosclerosis. IL-17 secreted by Th17 cells may aggravate the progression of the two diseases by elevating the levels of matrix metalloproteinases, which may damage the connective tissue. Treg cells reduce the activation of T cells and limit the development of inflammation by secreting anti-inflammatory factors and expressing coinhibitory molecules. Periodontal intervention may contribute to the treatment of atherosclerosis by reducing inflammatory markers in atherosclerosis. Many studies have shown that periodontitis and atherosclerosis may interact with each other, but further studies are needed to explore the concrete mechanism of the interaction between periodontitis and atherosclerosis.

Protection of intestinal immune barrier against ischemia/reperfusion injury in a swine model using anisodamine hydrobromide

Abstract Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. This study explored the protective effects of anisodamine hydrobromide (AH) on intestinal I/R injury caused by cardiopulmonary resuscitation (CPR) after cardiac arrest (CA). After successful CPR, minipigs were randomly divided into two groups (n = 8): saline and AH (4 mg/kg), and then treated with saline or AH via central venous injection, respectively. The same procedures without ventricular fibrillation initiation were conducted in the Sham group (n = 8). Levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) were measured at different time points (0, 0.5, 1, 2, 4, and 6 h) in serum and 6 h in gut associated lymphoid tissues (GALTs) after the return of spontaneous circulation (ROSC) to evaluate changes in the proportion of T-helper type 1 (Th1) and T-helper type 2 (Th2). Moreover, the positive culture rates of GALTs were examined to evaluate bacterial translocation. AH treatment markedly alleviated aberrant arterial blood gas and hemodynamics as well as intestinal macroscopic and morphological changes after CPR. Moreover, AH treatment significantly increased IFN-γ and decreased IL-4 in both serum and GALTs. Furthermore, AH treatment dramatically decreased positive bacterial growth in GALTs. AH treatment mitigated immunosuppression caused by intestinal I/R and protected the intestinal immune barrier against bacterial translocation, thereby reducing the risk of secondary intestinal infection

Changes and clinical significance of serum interleukin-9 and other T helper cell-related cytokines in patients with acute anterior uveitis / 中华实验眼科杂志

Objective:To explore the role of interleukin (IL)-9 and other T helper (Th) cell-related cytokines in the pathogenesis of acute anterior uveitis.Methods:A cross-sectional study was conducted.Thirty-six patients (36 eyes) with acute anterior uveitis who were treated at Gansu Provincial Hospital from May 2018 to May 2019 and 40 matched healthy subjects (40 eyes) who had no eye diseases or systemic diseases in the same period were enrolled as the acute anterior uveitis group and healthy control group, respectively.The disease severity of the subjects in the acute anterior uveitis group was graded and the subjects were divided into mild, moderate and severe groups according to the grading.Serum of all subjects was collected to determine the concentration of serum IL-9, IL-17, transforming growth factor-β 1 (TGF-β 1), interferon-γ (IFN-γ), IL-4, IL-35 and IL-22 by enzyme linked immunosorbent assay (ELISA) method.Spearman rank correlation analysis was used to evaluate the relationship between IL-9 concentration and other Th cell-related cytokines.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Gansu Provincial Hospital (No.2019-204). Written informed consent was obtained from each subject prior to any medical examination. Results:The serum levels of IL-9, IFN-γ, IL-4, TGF-β 1, IL-35 and IL-22 in the acute anterior uveitis group were significantly higher than those in the healthy control group, and the differences were statistically significant (all at P<0.05). There was no statistically significant difference in the concentration of IL-17 between the two groups ( U=704.500, P=0.872). The IL-9 concentration of patients with acute anterior uveitis in the mild, moderate and severe groups was 57.24 (47.47, 65.10), 71.68 (67.55, 78.91) and 114.01 (74.78, 139.30) ng/L, respectively, and the overall difference was statistically significant ( Z=8.766, P=0.012), and the IL-9 concentration of the mild group and the moderate group was significantly lower than that of the severe group (both at P<0.05). The concentration of IL-9 in the patients with acute anterior uveitis was positively correlated with the concentration of IL-17, TGF-β 1 and IL-35 ( rs=0.449, 0.517, 0.400; all at P<0.05), and no significant correlations were found between the concentration of IL-9 and the concentration of IFN-γ, IL-4 and IL-22 ( rs=0.293, 0.286, 0.316; all at P>0.05). Conclusions:IL-9 plays a role in promoting the immune inflammatory response in the occurrence and development of acute anterior uveitis, and it is closely related to Th17 and Treg cell-related cytokines (TGF-β 1, IL-35).

Changes and their significance of vitamin D, T helper cell 17 and regulatory T cells and associated cytokines in adolescents with multiple sclerosis / 中华实用儿科临床杂志

Objective:To investigate the function of the expression rate of vitamin D, T helper cell 17 (Th17) and regulatory T cells (Tregs) and the serum level of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) in the pathogenesis of adolescents with multiple sclerosis (MS).Methods:Thirty-eight adolescent patients diagnosed with MS in the Department of Pediatrics of the First Affiliated Hospital of Xinxiang Medical University from January 2010 to December 2020 were selected as the MS group, and 38 healthy adolescents matched with age and body mass index were selected as healthy control group.The level of 25-hydroxyvitamin D 3 [25-(OH)D 3] was measured by liquid chromatograph; the expression rates of Th17 and Tregs were measured by flow cytometry; the serum levels of TNF-α and MCP-1 were measured by immunofluorescence.SPSS 22.0 statistical software was adopted to analyze the differences between the above indicators and their correlation in the MS group and the healthy control group. Results:There was no difference in the level of 25-(OH)D 3 in peripheral blood between the MS group and the healthy control group( P>0.05). As for the MS group, the expression rate of Th17 was significantly higher than that in the healthy control group [(3.02±0.20)% vs.(1.99±0.16)%, t=12.03, P<0.05]; the expression rate of Tregs in peripheral blood was significantly lower than that in the healthy control group [(4.63±0.77)% vs.(5.10±0.90)%, t=14.65, P<0.05]; the ratio of Th17 to Tregs was significantly higher than that in the healthy control group (0.25±0.07 vs.0.17±0.05, t=16.89, P<0.05); the levels of TNF-α and MCP-1 in peripheral blood were higher than those in the healthy control group [(26.13±5.98) ng/L vs.(24.45±3.01) ng/L; (122.26±37.71) ng/L vs.(87.95±17.66) ng/L, t=1.986, 47.650, all P<0.05]. In the MS group, 25-(OH)D 3 in peripheral blood was not correlated with other test indicators; the levels of TNF-α and MCP-1 were higher in patients with relapsing or progressive disease than in patients with stable disease in remission [(17.49±3.94) ng/L vs.(14.45±3.81) ng/L; (90.42±23.06) ng/L vs.(77.55± 20.56) ng/L, t=1.990, 2.472, all P<0.05]; the expression rate of Th17 cells was positively correlated with the level of TNF-α and MCP-1 in peripheral blood ( r=0.478, 0.442, all P<0.05); the expression rate of Tregs was negatively correlated with the level of TNF-α and MCP-1 in peripheral blood ( r=-0.318, -0.356, all P<0.05). Conclusions:Th17 and Tregs may be involved in the immunopathological mechanisms in the pathogenesis of adolescents with MS; changes in associated cytokines may be involved in the regulation of Th17 and Tregs changes and the inflammatory response; Th17 and Tregs and associated cytokine changes may play an important role in the occurrence, progression, and relapse progression of MS as an immunopathological mechanism.

Regulation Effect and Clinical Efficacy of Addition and Subtraction Therapy of Jinkui Shenqiwan Combined with Buzhong Yiqitang on Immune Inflammatory Factors of Patients with Postmenopausal Osteoporosis and Deficiency of Spleen and Kidney / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang to postmenopausal osteoporosis （PMO） with deficiency of spleen and kidney， and to investigate its regulation effect on immune inflammatory factors. Method:One hundred and sixty patients were randomly divided into observation group and control group， with 80 cases in each group. Both groups got comprehensive western medicine treatment measures. Patients in control group additionally got Zhuanggu Zhitong capsule， 4 capsules/time， 3 times/day. Patients in observation group additionally got addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang， 1 dose/day. The treatment was continued for 24 weeks. Before and after treatment， lumbar L2-4 bone mineral density （BMD） was detected by Dual energy X-ray absorptiometry （DXA） and lumbar BMD was detected by quantitative CT （QCT）. Scores of traditional Chinese medicine（TCM） syndromes and Chinese osteoporosis-targeted quality of life questionnaire （COQOL） were graded. Levels of Estradiol （E₂）， type Ⅰ procollagen amino terminal pro peptide （PINP）， serum osteocalcin （OC）， osteoprotegerin （OPG）， type Ⅰ collagen cross-linked C-terminal peptide （S-CTX）， tartrate resistant acid phosphatase （TRACP） and urinary pyridinoline （PYD） were detected. Levels of CD4⁺ T cells， CD8⁺ T cells， interleukin-17 （IL-17）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， <italic>γ-</italic>interferon（IFN-<italic>γ</italic>） and interleukin-4 （IL-4） were calculated. The proportion of T helper cell （Th）17 and regulatory T cell （Treg） in CD4⁺ T cells was calculated. Besides， the safety was evaluated. Result:Bone density was detected by DXA in observation group， and its T-value and bone density detected by QCT were all higher than those in control group （<italic>P</italic><0.01）. After treatment， scores of TCM syndrome and COQOL were lower than those in control group （<italic>P</italic><0.01）. Levels of PINP， OC， S-CTX， TRACP and PYD/Cr were all lower than those in control group （<italic>P</italic><0.01）. Levels of OPG， CD8⁺ and Treg were higher than those in control group （<italic>P</italic><0.05）， levels of Th17， Th17/Treg， CD4⁺/CD8⁺， IL-17， TNF-<italic>α</italic> and IFN-<italic>γ </italic>were lower （<italic>P</italic><0.01）， and levels of IL-4 and E₂ were higher than those in control group （<italic>P</italic><0.01）. The clinical efficacy in observation group was better than that in control group （<italic>Z</italic>=2.103， <italic>P</italic><0.05）. Conclusion:On the basis of calcium and vitamin D supplementation， Jinkui Shenqiwan combined with Buzhong Yiqitang can improve levels of E₂ and bone density， reduce clinical symptoms， improve quality of life， regulate bone metabolism index and immune inflammation reaction， with better clinical efficacy and safety.

Polydatin Ameliorated Colonic Inflammation via Precluding Phosphorylation of PKCθ/STAT3 Pathway to Inhibit Th17 Cells in Mice with Ulcerative Colitis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect of polydatin on ulcerative colitis （UC） in mice and its regulation of protein kinase C<italic>θ</italic>（PKC<italic>θ</italic>）/signal transducer and activator of transcription 3（STAT3） signaling on T helper cell 17（Th17） and its mechanism in the treatment of UC. Method:The 32 male C57BL/6 mice were randomly divided into normal group， model group， polydatin group （0.045 g·kg^-1） and sulfasalazine group （0.5 g·kg^-1）. The UC model was established by giving 3% dextran sodium sulfate （DSS） solution to free drinking water in mice. Polydatin and sulfasalazine groups were given by gavage 0.5 h before modeling for 7 days. The normal group and model group were given the same amount of normal saline. After the last administration， the colonic tissue was taken and hematoxylin-eosin （HE） was used to observe the pathological changes of colonic tissue. Flow cytometry was used to detect the proportion of Th17 in the lamina propria of colonic mucosa. The expression of interleukin-17A （IL-17A） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Polydatin was added to CD4⁺T cells purified from spleen of C57BL/6 mice by magnetic-activated cell sorting （MACS） under the stimulation of cell stimulation cocktail <italic>in vitro </italic>in order to detect its impact on PKC<italic>θ</italic> and STAT3 phosphorylation. Result:Compared with normal group， the body weight was significantly decreased， and disease activity index （DAI） scores of the model group was significantly increased （<italic>P</italic><0.01）， the colonic mucosal epithelium was damaged and inflammatory cells infiltration in the mucosa and submucosa was obvious， the proportion of Th17 in the lamina propria of colonic mucosa was significantly increased （<italic>P</italic><0.01）， and the content of serum IL-17A was significantly increased （<italic>P</italic><0.01）. Compared with the model group， the weight and DAI score of polydatin and sulfasalazine groups were significantly improved （<italic>P</italic><0.01）， the degree of colon tissue damage was significantly improved， the proportion of Th17 in colon mucosa lamina propria was significantly decreased （<italic>P</italic><0.01）， and the content of IL-17A in serum was significantly decreased （<italic>P</italic><0.01）. <italic>In vitro</italic> experiments showed that polydatin could significantly inhibit the phosphorylation of PKC<italic>θ</italic> and STAT3 in Th17 （<italic>P</italic><0.01） as well as IL-17A secretion. Conclusion:Polydatin can improve the ulcerative colitis in mice via inhibiting the phosphorylation of PKC<italic>θ</italic> and STAT3 to preclude IL-17A secreting in Th17.

The relationship between Candida albicans infection and oral cancer / 口腔疾病防治

@#Oral cancer is one of the most common cancers that occur in the head and neck and can seriously affect the life span and living standard of oral cancer patients. Candida albicans （C. albicans） is the most common opportunistic pathogenic fungus in the oral cavity, shows pathogenicity and easily causes Candida infection when the host′s immune function is low. Recent studies have shown that C. albicans infection is closely related to oral cancer. This paper reviews the epidemiology of C. albicans infection in oral cancer patients, the influence of C. albicans infection on the occurrence and development of oral cancer and research on its mechanism. Existing studies have shown an increased risk of C. albicans infection in oral cancer patients, while C. albicans infection may promote the occurrence and development of oral cancer through mechanisms such as damaging the oral epithelium; producing carcinogens, including nitrosamine and acetaldehyde; and inducing a chronic inflammatory response and T helper cell 17 immune response. However, these mechanisms are still relatively superficial and lack sufficient direct evidence. In the future, additional in-depth studies are still needed to further clarify the cancer-promoting mechanisms of C. albicans and provide new ideas for the prevention and treatment of oral cancer.

Effect of type 2 diabetes mellitus on mandibular bone regeneration and the expression of T helper cell 17/regulat-ory T cell-related factors in mice / 华西口腔医学杂志

OBJECTIVES@#To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice.@*METHODS@#Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing.@*RESULTS@#HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM.@*CONCLUSIONS@#T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.

Effect of different orthodontic forces on the expression of T helper cell 17 cell-related cytokines in the pressure side of periodontal tissue in rats / 华西口腔医学杂志

OBJECTIVES@#This study aimed to explore the changes in the expression of the characteristic transcription factor retinoid related orphan receptor γt (RORγt) and the cytokine interleukin-17 (IL-17) of T helper cell 17 (Th17) in the pressure side of the periodontal tissue of rats under different orthodontic forces. Their effects on the expression of osteoprotegerin (OPG) and the quantity of osteoclast (OC) were also explored. The role of Th17 cell in alveolar bone remodeling under different forces was preliminarily investigated.@*METHODS@#A total of 108 rats were chosen and randomly divided into three groups. Mesial forces of 0, 50, and 100 g were loaded on the maxillary first molar in the three groups. The rats were executed at 0, 1, 3, 5, 7, and 14 days. The expression of RORγt mRNA was quantified by real-time quantitative polymerase chain reaction. The expression of IL-17 protein was quantified by enzyme linked immunosorbent assay. The expression levels of RORγt and OPG proteins were quantified, and the quantity of OC was counted via immunohistochemistry.@*RESULTS@#The expression levels of RORγt and IL-17 and the quantity of OC increased first and then decreased in the 50 and 100 g groups, and the peak values of the two groups were on days 5 and 7, respectively. The expression levels in the 50 g group basically recovered to normal level on day 14, while that in the 100 g group remained at a high level. The expression levels in the 50 g group were higher than those in the 0 g group and lower than those in the 100 g group. The expression of OPG in the 50 g group decreased first, then increased, and finally decreased. It basically recovered to normal level on day 14. The expression of OPG in the 100 g group decreased first and then increased. It remained at a high level on day 14. The expression in the 50 g group was significantly higher than that in the 0 g group on day 7, while the expression in the 100 g group was significantly higher than that in the 0 g group on day 14.@*CONCLUSIONS@#RORγt, IL-17, and OPG were expressed regularly over time under different orthodontic forces, indicating that Th17 participated in the process of bone resorption on the pressure side of periodontal tissue by secreting IL-17.

Therapeutic Effect of SPK1 Gene Transfected Adipose Derived Mesenchymal Stem Cells on Experimental Autoimmune Encephalomyelitis Mice and Its Effect on T Helper Cell 17/Regulatory T Cells Balance / 中国医学科学院学报

Objective To investigate the therapeutic effect of SPK1 gene transfected adipose derived mesenchymal stem cells(ADMSC)on experimental autoimmune encephalomyelitis mice and the effect on T helper cell 17(Th17)/regulatory T(Treg) cells balance. Methods EAE was induced by myelin oligodendrocyte glycoprotein 35-55 in mice.Totally 44 mice were randomly divided into four groups:normal control group(NC group),model group(EAE group),ADMSC group,and ADMSC-SPK1 group.Forty days after injection,the pathological changes of brain and spinal cord,Th17/Treg-related inflammatory markers in brain tissue,expressions of interleukin-17A(IL-17A)and forkhead box protein p3(Foxp3)in brain and spinal cord tissue,and flow cytometric results of spleen immune cells were detected. Results Forty days after the injection,serious inflammatory cell infiltration and demyelination occurred in the brain and spinal cord of EAE group,whereas demyelination and axonal injury were improved in ADMSC group and ADMSC-SPK1 group.Compared with EAE group,the ADMSC group and ADMSC-SPK1 group had significantly improved levels of IL-17A(

Role of bone marrow mesenchymal stem cells in different concentrations on regulatory T cell / T-helper cell 17 balance in rats / 中华危重病急救医学

Objective To explore the effects of bone marrow mesenchymal stem cells (BMSCs) in different concentrations on the balance of regulatory T cell / T-helper cell 17 (Treg / Th17). Methods BMSCs were isolated from SPF grade male Wistar rats with age of 3 weeks old and weight of 50 g. BMSCs were cultured and identified when they were expanded to the 4th generation. CD4+ T lymphocytes were isolated from SPF grade male Wistar rat with age of 6 weeks old and weight of 200 g and assayed for cell purity by flow cytometry. BMSCs were divided into 0.5-fold concentration group, basal concentration group, 2-fold concentration group and 4-fold concentration group by their concentrations of 1×105/well, 2×105/well, 4×105/well and 8×105/well, which were cultured with CD4+ T lymphocytes for 72 hours, respectively. Then the proportion of Treg cells and Th17 cells in each group was detected by flow cytometry, and cytokines were detected by cytometric bead array. Results The purities of BMSCs and CD4+ T lymphocytes were both higher than 95%. In the co-culture of BMSCs and CD4+ T lymphocytes, the proportions of Treg cells were statistically different among different concentration groups of BMSCs (F = 10.071, P = 0.001), in which BMSCs in 2-fold concentration group had the strongest ability to promote the Treg cells proliferation. The proportion of Treg cells in 2-fold concentration group was significantly higher than that in 0.5-fold concentration group, basal concentration group and 4-fold concentration group [(9.24±2.68)% vs. (3.87±0.38)%, (5.16±1.69)%, (3.86±0.36)%, all P < 0.01]. The level of interleukin-10 (IL-10) was lowest in 0.5-fold concentration group, and it was significantly lower than that in basal concentration group, 2-fold concentration group and 4-fold concentration group (ng/L: 39.80±14.48 vs. 148.43±64.49, 156.40±59.27, 126.92±42.95, all P < 0.05). Transforming growth factor-β (TGF-β) was the highest in basal concentration group, and it was significantly higher than that in 0.5-fold concentration group, 2-fold concentration group and 4-fold concentration group [ng/L: 3.17 (1.88, 5.74) vs. 0.71 (0.32, 1.38), 1.22 (0.47, 2.97), 0.52 (0.37, 1.23), all P < 0.05]. The proportions of Th17 cells were statistically different among the different concentration groups (F = 21.069, P = 0.000), with the highest proportion in basal concentration group which was significantly higher than that in 0.5-fold concentration group or 4-fold concentration group [(0.89±0.08)% vs. (0.64±0.15)%, (0.37±0.10)%, both P < 0.01], but no significant difference was found as compared with 2-fold concentration group [(0.83±0.06)%, P > 0.05]. However, the expressions of IL-17 and IL-6 were not different among the different concentration groups respectively (IL-17: χ2 = 0.550, P = 0.760;IL-6: χ2 = 0.010, P = 0.995). Conclusions BMSCs in moderate concentrations [(2-4)×105/well] could promote proliferation both in Treg cells and Th17 cells, but no change could be found in higher concentrations of BMSCs (8×105/well). However, the changes in related cytokines were not synchronized with Treg / Th17 cells.

Research progress on the relationship between T helper cell 17, interleukin-17 and lung cancer / 中国胸心血管外科临床杂志

@#A new independent subtype CD4+ T cell which massively secreted interleukin-17 (IL-17) was found at the beginning of the 21st century, and thus it was named as T helper cell 17 (Th17 cell). With the progress of the research in recent years, Th17 cells were found to be widely involved in a variety of the human diseases such as autoimmune diseases, infections and tumors through secretion of IL-17. The relationship between Th17 cells, IL-17 and the occurrence, development and prognosis of lung cancer was reviewed.