AbstractToll-like receptor 3 (TLR3), a receptor for viral double strain RNA (dsRNA), mediates anti-viral immune response by activating the innate immunity and cross-priming CD8+ T cells. TLR3 agonists can directly trigger apoptosis in human cancer cells, and have been used as adjuvants to treat cancer patients with the aim of inducing an IFN-dependent immune response. In this study, we examined the effect of TLR3 activation on the metastasis of nasopharyngeal carcinoma (NPC). We found that NPC cells expressed TLR3 gene transcript and protein. TLR3 activation down-regulated the expression of chemokine receptor CXCR4 in a dose-dependent manner, and inhibited cell migration in response to CXCR4 ligand stromal cell-derived factor-1α (SDF-1α) in chemotaxis assays. Furthermore, TLR3 activation significantly reduced the capacity of NPC cells to form metastasis in draining lymph nodes when injected in athymic mice. The anti-metastasis activity of endogenous human TLR3 expression in cancer cells reveals a novel aspect of the multiple-faced TLR biology, which may open new clinical prospects for using TLR3 agonists to control cancer metastasis in selected cancers.
IL-17 is a novel inflammatory factor, mainly generated by Th17 cells.It can induce other inflammatory cytokine and chemokine production to stimulate neutrophil recruitment and activation contributing inflammatory reaction and immune responses.With The deep research of IL-17, it is found that it may play an important role in encephalitis, epilepsy, autoimmune disease, brain tumors and other diseases of nervous system.
Key words:
Interleukin-17; Inflammation; Nervous system disease
The aim of the present study was to explore whether an ultra-filtration extract from Xin Mai Jia (XMJ), a Chinese medicinal formulation, has a protective effect on human aortic smooth muscle cell (HASMC) injury models induced by hydrogen peroxide (H2O2), and to consider the mechanism and efficacy of the therapeutic action of XMJ on atherosclerosis. HASMCs were injured by H2O2 and then exposed to various concentrations of XMJ. The morphological changes, growth, proliferation, migration and cytokine release of HASMCs were detected using 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), an enzyme-linked immunosorbent assay and a scratch adhesion test. H2O2 significantly promoted the proliferation of HASMCs. The ultra-filtration extract from XMJ was observed to significantly attenuate the morphological changes of injured HASMCs, reduce the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin (IL)-1, IL-6 and nuclear factor (NF)-κB, and increase the expression levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP). XMJ has clear anti-inflammatory and antioxidant effects, and significantly inhibits the proliferation and migration of HASMCs.
// Xi Pan 1, 2, 3 , Binyuan Jiang 1, 2 , Jianhao Liu 4 , Juan Ding 3 , Yuehui Li 1, 2 , Ruili Sun 1, 2 , Li Peng 1, 2 , Changfei Qin 1, 2 , Shujuan Fang 1, 2 and Guancheng Li 1, 2 1 The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410008, China 2 Cancer Research Institute, Central South University, Changsha 410078, China 3 Xiangya Third Hospital, Central South University, Changsha 410078, China 4 School of Pharmaceutical Sciences of Central South University, Changsha 410078, China Correspondence to: Guancheng Li, email: ligc61@csu.edu.cn Keywords: stanniocalin-1 (STC1), cell apoptosis, cervical cancer, NF-κB, phospho-P65 (Ser536) Received: November 22, 2016 Accepted: March 11, 2017 Published: May 05, 2017 ABSTRACT Stanniocalin-1 (STC1) is a secreted glycoprotein hormone and involved in various types of human malignancies. Our previous studies revealed that STC1 inhibited cell proliferation and invasion of cervical cancer cells through NF-κB P65 activation, but the mechanism is poorly understood. In our studies, we found overexpression of STC1 promoted cell apoptosis while silencing of STC1 promoted cell growth of cervical cancer. Phospho-protein profiling and Western blotting results showed the expression of NF-κB related phosphorylation sites including NF-κB P65 (Ser536), IκBα, IKKβ, PI3K, and AKT was altered in STC1-overexpressed cervical cancer cells. Moreover, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA could decrease the protein content of phospho-P65 (Ser536), phospho-IκBα, phospho-AKT and phospho-IKKβ while increasing the level of P65 compared to STC1 overexpression groups in cervical cancer cells. Also, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA elevated the percentage of apoptosis and suppressed the G1/S transition in those cells. Additionally, STC1 level was decreased in cervical cancer, especial in stage II and III. The results of immunohistochemistry for the cervical cancer microarray showed that a lower level of STC1, phospho-PI3K and P65 protein expression in tumor tissues than that in normal tissues, and a higher level of phospho-P65 protein expression in tumor tissues, which is consistent with the results of the Western blotting. These data demonstrated that STC1 can promote cell apoptosis via NF-κB phospho-P65 (Ser536) by PI3K/AKT, IκBα and IKK signaling in cervical cancer cells. Our results offer the first mechanism that explains the link between STC1 and cell apoptosis in cervical cancer.
Despite recent research highlighting the critical function of RIO kinase 3 (RIOK3) in a variety of malignancies, a comprehensive evaluation of RIOK3 in human tumors is absent. Our study helps to clarify the molecular mechanism of RIOK3 in carcinogenesis from multiple perspectives.Our research looked into the potential oncogenic role of RIOK3 in 33 cancers using TCGA (The Cancer Genome Atlas), GTEx (Genotype-Tissue Expression Project), GEO (Gene Expression Omnibus) datasets, and several bioinformatics tools.RIOK3 expression in tumors is disordered compared to normal tissue, and it is highly linked with the level of MMR (Mismatch repair) gene mutations and DNA methyltransferase expression. According to univariate survival analysis, it could be used as an independent prognostic factor. Further investigation demonstrated that RIOK3 expression was correlated with cancer-associated fibroblast, neutrophil, and endothelial infiltration levels in kidney cancer and was positively correlated with the expression of immune checkpoint markers in different cancers. The functional pathways of RIOK3 also included cell-cell adhesion, protein phosphorylation, and innate immune-related functions.These findings suggest that RIOK3 could be used as an immunological and prognostic biomarker in various malignant tumors.
Tripalmitoyl-S-glycero-Cys-(Lys) 4 (Pam3CSK4) interacted with TLR2 induces inflammatory responses through the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signal pathway. Rapamycin can suppress TLR-induced inflammatory responses; however, the detailed molecular mechanism is not fully understood. Here, the mechanism by which rapamycin suppresses TLR2-induced inflammatory responses was investigated. It was found that Pam3CSK4-induced pro-inflammatory cytokines were significantly down-regulated at both the mRNA and protein levels in THP-1 cells pre-treated with various concentrations of rapamycin. Inhibition of phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT) signaling did not suppress the expression of pro-inflammatory cytokines, indicating that the immunosuppression mediated by rapamycin in THP1 cells is independent of the PI3K/AKT pathway. RT-PCR showed that Erk and NF-κB signal pathways are related to the production of pro-inflammatory cytokines. Inhibition of Erk or NF-κB signaling significantly down-regulated production of pro-inflammatory cytokines. Additionally, western blot showed that pre-treatment of THP-1 cells with rapamycin down-regulates MAPKs and NF-κB signaling induced by Pam3CSK4 stimulation, suggesting that rapamycin suppresses Pam3CSK4-induced pro-inflammatory cytokines via inhibition of TLR2 signaling. It was concluded that rapamycin suppresses TLR2-induced inflammatory responses by down-regulation of Erk and NF-κB signaling.
Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated.Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension.Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6–12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure.Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension.
Abstract Background Human papillomavirus (HPV) infection can cause cervical and other cancers including cancer of vulva, vagina, penis, anus, or oropharynx. However, data concerning the prevalence and genotype distribution of HPV among women are limited in northern Henan Province of China. This study aimed to make an investigation on the current prevalence and genotype distribution of HPV among women and provided comprehensive data to guide HPV-based cervical cancer prevention in northern Henan Province. Methods A total of 15616 women aged 16 to 81 years who attended the department of gynecology of Xinxiang central hospital between January 2018 and December 2019 were enrolled in this study. HPV DNA was detected by PCR method followed by HPV type-specific hybridization. The overall prevalence, age-specific prevalence and genotype distribution of HPV were investigated. Results The overall HPV prevalence was 19.7% among women in northern Henan Province. Single, double and multiple HPV infections accounted for 13.7%, 4.3% and 1.8% of the total cases, respectively. HPV prevalence was 41.8% among women aged 16 to 19 years, 21.1% among women aged 20 to 29 years, 18.1% among women aged 30 to 39 years, 17.7% among women aged 40 to 49 years, 20.8% among women aged 50 to 59 years, 22.9% among women more than 60 years. HPV infection rates differed significantly across different age groups. Most infections were caused by high-risk HPV (HR-HPV) and single genotype HPV infection was the most common pattern. The most common HR-HPV genotype was HPV16, followed by HPV52, HPV58, HPV53 and HPV39. The most common low-risk HPV (LR-HPV) genotype was HPV6, followed by HPV61, HPV81, HPV54 and HPV11. Conclusions HPV infection is common among women in northern Henan Province. The highest infection prevalence was found in women less than 20 years old. The 9-valent HPV vaccine for routine vaccination is strongly recommended in northern Henan Province.
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