Prognosis comparison between hepatocellular carcinoma patients with microvascular invasion who received hepatectomy alone and those who underwent early PA-TACE: a retrospective cohort study.

Background: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) can achieve longer overall survival (OS) and disease-free survival (DFS) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). We investigated whether this treatment strategy could benefit these patients by mediating the dysfunctional immunological status. Therefore, a retrospective cohort study was conducted to investigate the effect of early PA-TACE in HCC patients with MVI by measuring the levels of T helper cell 17 (Th17) and regulatory T cell (Treg). Methods: This study retrospectively included 472 patients with HCC undergoing hepatectomy between December 2015 and December 2018, and 115 patients with MVI confirmed by postoperative pathology were enrolled and divided into two groups of TACE group and non-TACE group according to whether TACE was performed. HCC patients with MVI. The proportion of Treg and Th17 cells in peripheral blood was measured one day before and four weeks after TACE. All patients in the two groups were followed up until death or until the study ended in December 2023. The rates of OS and progression-free survival (PFS) in patients with MVI were compared between those who received hepatectomy alone and those who underwent early PA-TACE. Results: Among 115 HCC patients with MVI from 472 patients, the study enrolled 51 patients with PA-TACE into the TACE group and 42 patients without TACE into the non-TACE group. There were no statistical differences in baseline data between the two groups (all P>0.05). The frequency of Treg among CD4+ T cells in HCC patients with PA-TACE was significantly lower than baseline (7.34%±3.61% vs. 5.82%±2.76%, P<0.001), and the frequency of Th17 among CD4+ T cells in these patients was significantly higher than baseline (0.49%±0.28% vs. 0.50%±0.25%, P<0.001). Among all the patients, the median OS was 61.8 months. The OS rate and PFS rate at 12, 36, and 60 months in the TACE group were significantly higher than those in the non-TACE group (all P<0.05). Conclusions: PA-TACE may have roles in improving survival outcomes, and restoring immune homeostasis in HCC patients with MVI after hepatectomy.

Yiqi Jiedu Xiaoying Decoction Improves Experimental Autoimmune Thyroiditis in Rats by Regulating Th17/Treg Cell Balance.

BACKGROUND: Experimental autoimmune thyroiditis (EAT) is a widely used animal model to study the pathogenesis and treatment of autoimmune thyroid diseases. Yiqi Jiedu Xiaoying Decoction (YJXD) is a traditional Chinese medicine formula with potential immunomodulatory effects. In this study, we investigated the therapeutic effects of YJXD on EAT in rats and explored its underlying mechanisms. METHODS: Female Wistar rats were induced to develop EAT by immunization with thyroglobulin (Tg) and taken sodium iodide water (0.05%) and then treated with YJXD or sodium selenite. HE staining was used to observe the pathological changes of thyroid tissue in EAT rats. Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expression levels of Th17- and Treg-related cytokines and thyroid autoantibody were determined by enzyme-linked immunosorbent assay (ELISA). The expression of Th17- and Treg-related transcriptional factors was detected by real-time polymerase chain reaction (RT-PCR) and Immunohistochemistry (IHC). RESULTS: Our results demonstrated that treatment with YJXD significantly attenuated the severity of EAT, as evidenced by reduced thyroid gland inflammatory infiltration and decreased serum thyroglobulin autoantibody levels. Importantly, YJXD treatment effectively modulated the Th17/Treg cell balance by suppressing Th17 cell differentiation and promoting Treg cell expansion. Moreover, YJXD was also found to regulate the expression levels of Th17- and Tregrelated cytokines and transcriptional factors, further supporting its immunomodulatory effects in EAT. CONCLUSION: YJXD exerted therapeutic effects on EAT by regulating the Th17/Treg cell balance, modulating the production of Th17- and Treg-related cytokines and the expression of transcriptional factors.

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.

Changes in the balance of Th17/Treg cells and oxidative stress markers in patients with HIV­associated pulmonary tuberculosis who develop IRIS.

Tuberculosis (TB) is the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection and is one of the primary causes of death from AIDS. The increased accessibility to highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of patients with HIV infection. However, following ART, rapid restoration of the immune system leads to immune reconstitution inflammatory syndrome (IRIS). Oxidative stress and innate immunity play a role in TB-associated IRIS (TB-IRIS). The present study investigated the changes that occur in oxidative stress markers and T helper (Th)17/regulatory T (Treg) cell balance and their significance in IRIS patients with HIV-associated pulmonary TB. A total of 316 patients with HIV-associated pulmonary TB were treated with HAART and followed up regularly for 12 weeks. Those who developed IRIS were included in the IRIS group (n=60), while the remaining patients were included in the non-IRIS group (n=256). The changes in plasma oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA) were detected with the ELISA, and the ratio of Th17 to Treg cells in whole blood were analyzed before and after treatment through the flow cytometric assay. Following treatment, MDA and Th17 cells levels were significantly increased while SOD and Treg cells levels were decreased in the IRIS group (P<0.05) compared with before treatment. In the non-IRIS group, a non-significant decrease was observed in SOD levels (P>0.05), while the MDA levels significantly decreased compared with before treatment (P<0.05) and the Th17 and Treg cells levels were both significantly increased (P<0.05). After treatment, compared with the non-IRIS group, the IRIS group showed a significant increase in MDA and Th17 cells and decrease in SOD and Treg cells levels (P<0.05). In addition, Th17 cells levels were positively correlated with MDA but negatively correlated with SOD levels. Treg levels were negatively correlated with MDA and positively correlated with SOD levels (P<0.05). The area under the curve values of serum MDA and SOD, Th17 and Treg levels predicting the occurrence of IRIS were 0.738, 0.883, 0.722 and 0.719, respectively (P<0.05). These results indicated that the above parameters have certain diagnostic value for the occurrence of IRIS. The occurrence of IRIS in patients with HIV-associated pulmonary TB may be associated with oxidative stress and Th17/Treg cell imbalance.

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.

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.

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.

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 into Th9 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.

Stem cells from exfoliated deciduous teeth transplantation ameliorates Sjögren's syndrome by secreting soluble PD-L1.

Mesenchymal stem cell transplantation (MSCT) regulates immune cells, and is a promising therapeutic approach for treating autoimmune diseases. Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population from the cranial neural crest with high self-renewal, multipotent differentiation, and superior immunomodulatory properties. However, the mechanisms by which SHED can treat autoimmune diseases remain unclear. Sjögren's syndrome (SS) is an autoimmune disease histologically characterized by high lymphocytic infiltration in the salivary and lacrimal glands that results in dryness symptoms. This study explores the potential of systemic transplantation of SHED to ameliorate SS-induced dryness symptoms in mice. Overall, SHED could rescue the balance of regulatory T cell (Treg)/T helper cell 17 (Th17) in the recipient SS mice. Mechanistically, SHED promoted Treg conversion and inhibited Th17 function via paracrine effects, which were related to the secretion of soluble programmed cell death ligand 1 (sPD-L1). Moreover, it directly induced Th17 apoptosis via cell-cell contact, leading to the up-regulation of Treg and down-regulation of Th17 cells. In summary, SHED-mediated rescue of Treg/Th17 balance via the sPD-L1/PD-1 pathway ameliorates the gland inflammation and dryness symptoms in SS mice. These findings suggest that SHED are a promising stem cell source for the treatment of autoimmune diseases in the clinical setting.

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.

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.

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.

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.

Interleukin 2 Ameliorates Autoimmune Neuroinflammation by Modulating the Balance of T Helper 17 Cells and Regulatory T Cells in Mouse.

OBJECTIVE: Multiple sclerosis (MS) is a progressive autoimmune-mediated inflammation of the central nervous system (CNS), and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study the pathogenesis of MS. IL-2 has been considered as both a T cell growth factor and an anti-inflammatory cytokine. In the present study, we investigated the effects of a low dose IL-2 treatment on mouse EAE therapy. METHOD: The expression of IL-2 and IL-2 receptor were predicted using public microarray data and verified by real-time PCR and ELISA in mouse EAE model. Mice were injected with Myelin Oligodendrocyte Glycoprotein (35-55)(MOG35-55) subcutaneously to induce EAE model. IL-2 treatment was initiated during 5 consecutive days from day 15 post MOG35-55 immunization. Flow cytometry was applied to investigate the proportions of Th17 and Treg cells. ELISA was used to detect the concentrations of IL-17a, IFNr, IL-10 and TGFb. RESULTS: In this study, we showed that the IL-2 treatment ameliorates the clinical severity of EAE. Flow cytometry results indicated that the therapeutic effect was related to a reduction of Th17 cells and an expansion of Treg cells in the EAE spinal cord. In vitro experiments also confirmed the anti-inflammatory effect of IL-2 in EAE-reactivated T cells. CONCLUSION: Low-dose IL-2 is a potential therapeutic strategy for EAE and MS.

Selective activation of cannabinoid receptor 2 regulates Treg/Th17 balance to ameliorate neutrophilic asthma in mice.

BACKGROUND: The cannabinoid receptor 2 (CNR2) plays a critical role in relieving asthma, with the mechanism still unclear. We aimed to investigate the mechanism of the CNR2 agonist (ß-caryophyllene, ß-Car) in regulating the balance of regulatory T cells (Treg) and T helper cell 17 (Th17) and thus its role in asthma. METHODS: The study group of 50 pathogen-free female BALB/c mice were randomly divided at 6-8 weeks old into five groups of Control, Asthma, Asthma + ß-Car (10 mg/kg), Asthma + ß-Car + SR144528 (specific CNR2 antagonist, 3 mg/kg), and Asthma + ß-Car + CMD178 (inhibitor of Treg cell, 10 mg/kg). ELISA was conducted to evaluate the main inflammatory cytokines [interleukin (IL)-6, IL-8, and tumor necrosis factor-α], and those secreted by Treg (transforming growth factor-ß and IL-10), and Th17 (IL-17A and IL-22). Markers of Treg and Th17 cells were assessed by flow cytometry. In vitro, the CD4+ T cells were sorted and directed to differentiate to Treg and Th17 cells. The expression levels of CNR2, STAT5 and JNK1/2 were investigated by western blot and immunofluorescence assay. RESULTS: ß-Car relieved neutrophilic asthma severity in mice by elevating the marker genes' expression of Treg and inhibiting those of Th17, causing an increased proportion of Treg to Th17. ß-Car also promoted the directed differentiation of CD4+ T cells into Treg, but not Th17. Activation of the CNR2 regulated the Treg/Th17 balance and relieved neutrophilic asthma possibly through promotion of phosphorylation of STAT5 and JNK1/2. CONCLUSIONS: The effect of the selective CNR2 agonist activating STAT5 and JNK1/2 signaling was to change the Treg/Th17 balance and reduce the inflammatory reaction, thus ameliorating neutrophilic asthma in a mouse model.

[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].

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.

Mechanism of Xiaoying Daotan decoction in treating Hashimoto's thyroiditis based on the Notch/Treg/Th17 pathway.

BACKGROUND: The study created mice model of Hashimoto's thyroiditis (HT) and induced thyroid inflammatory cell lines, exploring the mechanism of Xiaoying Daotan decoction on HT. METHODS: Divided HT mice models into model group (0.2 mL saline), Western medicine group (0.2 mL levothyroxine sodium tablets), traditional Chinese medicine group (0.2 mL Xiaoyin Daotan prescription), and Notch protein inhibition group (0.2 mL Xiaoyin Daotan prescription). After treatment, serum Notch protein expression and T cell (Treg)/T helper cell 17 (Th17) cytokines levels were detected through Enzyme linked immunosorbent assay (ELISA). Use real-time qualitative polymerase chain reaction detected Notch protein expression. Thyroid inflammatory cell lines were induced and divided into 5 groups: blank group, iNotch group (knocking down the Notch protein gene of thyroid inflammatory cells), NC group (Notch protein carrier negative control group), iNotch + DS group and DS group (knocking down the Notch protein gene of thyroid inflammatory cells). The cells were treated with serum containing Xiaoying Daotan decoction. After culture, detected Notch protein expression level and Treg/Th17 cytokine level in each group. RESULTS: For the animal experiment, the serum Notch protein expression, the serum levels of key activating proteins Signal Transducer and Activator of Transcription 3 (STAT3), RAR-related orphan receptor gamma T (RORγt), and interleukin (IL)-22 of Th17 cells of mice in the model group was significantly higher than that of the other groups. Compared with the model group and Western medicine group, the serum transforming growth factor-ß (TGF-ß) level of the mice in the traditional Chinese medicine group and the Notch protein inhibition group was significantly higher. All the differences were statistically significant (P<0.05). For the cell experiment, the ß-actin value of Notch protein in thyroid inflammatory cell genes was significantly downregulated and the key activation protein of Treg was significantly upregulated in iNotch + DS group and DS group compared with the other 3 groups. Levels of Th17 key activating proteins STAT3, IL-17, and IL-22 in the iNotch group, iNotch + DS group, and DS group were lower than those of the blank group and NC group, both with statistically significant difference (P<0.001). CONCLUSIONS: The mechanism of Xiaoying Daotan decoction on HT could be related to the immune inflammatory response of the Treg/Th17 cell axis mediated by the Notch protein pathway.

Increased expression of T helper 17 cells and interleukin-17 in atopic dermatitis: a systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with genetic susceptibility and recurrent attacks. Research examining the etiology of this disease has mainly focused on environmental factors and immunity, with immune disorders believed to be the main factor in the occurrence and development of AD. While some studies have demonstrated that increased proportion of T helper 17 (Th17) cells in the lesions of specific dermatitis mouse models, the expression of Th17 cells and interleukin (IL)-17 in patients with AD remains controversial. METHODS: Related literatures were retrieved from English databases including PubMed, Embase, and Ovid-Medline. Literatures published from the establishment of the database to April 2021 were identified using the following keywords: AD, T helper cell 17 (Th17 cell), and interleukin 17 (IL-17). Review Manager5.3 software was adopted for meta-analysis. RESULTS: A total of 8 studies, involving 1,147 subjects, related to the pathogenesis of AD were included in this meta-analysis. The analysis revealed that the expression of Th17 cells in patients with AD was higher than that in healthy patients (P<0.00001), and the serum expression of IL-17 was also elevated in patients with AD compared to healthy participants (P=0.0001). DISCUSSION: A total of 8 publications related to the pathogenesis of AD were analyzed. The meta-analysis found that patients with AD had higher expressions of Th17 cells and IL-17 compared to healthy subjects, suggesting that AD may be related to Th17 cells and IL-17.

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.

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.

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.

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.