作者机构：
[Hu Yang; Xiao Jianhua] Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Co, Inst Pathogen Biol, Hengyang Med Coll,Hunan Prov Cooperat Innovat Ctr, Hengyang 421001, Hunan, Peoples R China.;[Hu Yang; Yang Xuefeng] Univ South China, Affiliated Nanhua Hosp, Dept Gastroenterol, Hengyang 421002, Hunan, Peoples R China.;[Xiao Jianhua] Univ South, Inst Pathogen Biol, Med Coll, 28W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xiao Jianhua] U;Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Co, Inst Pathogen Biol, Hengyang Med Coll,Hunan Prov Cooperat Innovat Ctr, Hengyang 421001, Hunan, Peoples R China.;Univ South, Inst Pathogen Biol, Med Coll, 28W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
CTL(cytotoxic T lymphocyte);hepatocellular carcinoma;interleukin;tumor microenvironment
摘要：
Hepatocellular carcinoma (HCC) is a primary liver cancer with high morbidity and mortality that is often accompanied by immune system disorders and local lymphocyte infiltration. Tumor-infiltrating lymphocytes, cancer cells, stromal cells, and the numerous cytokines they produce, such as chemokines, interferons, tumor necrosis factors, and interleukins, collectively constitute the tumor microenvironment. As a main type of immune effector, interleukin plays opposing roles in regulating tumor cell progression, adhesion, and migration according to its different subtypes. Many reports have concentrated on the roles that interleukins play in HCC, but understanding them systematically remains challenging. This study reviewed the current data to comprehensively summarize the relationships between HCC progression and human interleukin gene families.
摘要：
Aims & ScopeFoundations of Chemistry is an international journal which seeks to provide an interdisciplinary forum where chemists, biochemists, philosophers, historians, educators and sociologists with an interest in foundational issues can discuss conceptual and fundamental issues which relate to the `central science' of chemistry. Such issues include the autonomous role of chemistry between physics and biology and the question of the reduction of chemistry to quantum mechanics. The journal will publish peer-reviewed academic articles on a wide range of subdisciplines, among others: chemical models, chemical language, metaphors, and theoretical terms; chemical evolution and artificial self-replication; industrial application, environmental concern, and the social and ethical aspects of chemistry's professionalism; the nature of modeling and the role of instrumentation in chemistry; institutional studies and the nature of explanation in the chemical sciences; theoretical chemistry, molecular structure and chaos; the issue of realism; molecular biology, bio-inorganic chemistry; historical studies on ancient chemistry, medieval chemistry and alchemy; philosophical and historical articles; and material of a didactic nature relating to all topics in the chemical sciences. Foundations of Chemistry plans to feature special issues devoted to particular themes, and will contain book reviews and discussion notes. Audience: chemists, biochemists, philosophers, historians, chemical educators, sociologists, and other scientists with an interest in the foundational issues of science.Coverage in the Journals@Ovid database begins with the March 1999 issue.
期刊：
International Journal of Clinical and Experimental Medicine,2019年12(2):1535-1544 ISSN：1940-5901
通讯作者：
Xiao, Jianhua
作者机构：
[Li, Lifang; Xiao, Jianhua] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 Changsheng Rd, Hengyang 421001, Peoples R China.;[Li, Lifang; Zou, Yan; Yan, Dewen; Lin, Guangfeng; Zhang, Tingji] Second Peoples Hosp Shenzhen, Shenzhen 518037, Peoples R China.
通讯机构：
[Xiao, Jianhua] U;Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 Changsheng Rd, Hengyang 421001, Peoples R China.
关键词：
Type 2 diabetes mellitus;Baihu decoction;adipose tissue;chronic inflammation;CD14
摘要：
The incidence of Type 2 diabetes mellitus (T2DM) has increased worldwide. This study investigated the effect of a herbal extract, named as Baihu decoction (BHD), in treating T2DM by using mouse adipose cells and a mouse T2DM model. Mouse 3T3-L1 preadipocytes were cultured in DMEM culture medium and used for experiments when about 90% fat-differentiated cells were mature. The KM male mouse diabetes model was established by injecting streptozotocin. Thirty two KM T2DM mice were randomly divided into 4 groups, with 8 mice in each group. Enzyme-linked immunosorbent assays (ELISA) and Reverse Transcription-quantitative PCR (RT-real time-PCR) were performed to investigate the levels of inflammatory factors and adipokines related to diabetes and their mRNA levels. Western blot experiments were carried out to determine levels of a series of proteins. BHD reduced inflammatory responses induced by lipopolysaccharide in mouse adipose cells and repressed the activity of the CD14/TLR4-NF-kappa B signal pathway. Our siRNA experimental results demonstrated that decreased CD14 gene expression reduced the levels of inflammation significantly. The animal experimental results indicated that BHD has an effective effect on reduction of blood sugar level of T2DM mice. Furthermore, this anti-diabetic effect was due to inhibition of the activity of the CD14/TLR4-NF-kappa B signal pathway, especially CD14. BHD has anti-diabetic effect both in vitro and in vivo by down-regulating the activity of the CD14/TLR4-NF-kappa B signaling pathway, especially CD14.
摘要：
Objective: Zymosan A is a type of fungus polysaccharide that is derived from the cell wall of yeast and induces immune responses associated with fungal infection. In this study, our aim was to observe the expression and degradation of the following cytokines: TNF-alpha, CXCL1, IL-10 and IL-23a. These cytokines were induced by Zymosan A via primary peritoneal macrophages (pM Phi s), and they had more AU-rich elements (ARE) within their 3'-UTR mRNA sequence. Additionally, we would like to explore the mechanism underlying the p38 regulation of the ARE-mRNA stability of the related cytokines in the MAPK signaling pathway. Methods: Primary peritoneal macrophages (pM Phi s) were isolated and purified from C57 mice and stimulated with Zymosan A. The mRNA expressions of TNF-alpha, CXCL1, IL-10 and IL-23a that were induced by Zymosan A were detected by Real-time PCR, and the mRNA 3'-UTR sequences of these cytokines were analyzed using bio-informatic methods. The activation of MAPK signaling pathways and blocking experiments in pM Phi s treated with Zymosan A were identified by western blot, and the change in TTP, which is a type of RNA binding protein, was observed through in vitro enzymatic activity experiments. Results: Zymosan A induces a high expression of TNF-alpha, CXCL1, IL-10 and IL-23a and activates the MAPK signaling pathway through the phosphorylation of p38, ERK, and JNK and the RNA binding protein TTP. Bio-informatic analysis showed that the mRNA 3' UTR region of the related cytokines contained numerous AU-rich element (ARE) sequences. In the MAPK signaling pathway activated by Zymosan A, the ERK inhibitor PD98059 and the JNK inhibitor SP600125 had no effect on the ARE-mRNA stability of these cytokines. Conversely, the p38 inhibitor SB202190 effectively inhibited the phosphorylation of the downstream MK2 and TTP within the p38 signaling pathway and quickly degraded the mRNA of the above cytokines. An in vitro enzymatic activity experiment also proved that the phosphorylation of TTP disappeared after the treatment of lambda PP, which is a type of phosphoesterase. Conclusions: Zymosan A induces the high expression of TNF-alpha, CXCL1, IL-10 and IL-23a, which contain ARE-mRNA, and effectively activates MAPK signaling pathways through the phosphorylation of p38, ERK and JNK. In MAPK signaling pathways, p38 plays an important role about the mRNA stability and can enhance the ARE-mRNA stability of the above cytokines, the mechanism of its effect may be that p38 phosphorylate the downstream MK2 and TTP, which leads to the phosphorylated TTP can't combine with the mRNA ARE sequence and degrades the mRNA effectively.
关键词：
Toll-like receptor (TLR);mTOR;vaccine;hepatitis B virus (HBV);hepatitis C virus (HCV);adjuvant;c-fos
摘要：
Although IL-12 plays a critical role in priming Th1 and cytotoxic T lymphocyte (CTL) responses, Toll-like receptor (TLR) signaling only induces low amounts of IL-12 in dendritic cells and macrophages, implying the existence of stringent regulatory mechanisms. In this study, we sought to uncover the mechanisms underlying TLR-induced IL-12 expression and the Th1 response. By systemic screening, we identified a number of protein kinases involved in the regulation of TLRinduced IL-12 expression. In particular, PI3K, ERK, and mTOR play critical roles in the TLR-induced Th1 response by regulating IL-12 and IL-10 production in innate immune cells. Moreover, we identified c-fos as a key molecule that mediates mTOR-regulated IL-12 and IL-10 expression in TLR signaling. Mechanistically, mTOR plays a crucial role in c-fos expression, thereby modulating NFκB binding to promoters of IL-12 and IL-10. By controlling the expression of a special innate gene program, mTOR can specifically regulate the TLR-induced T cell response in vivo. Furthermore, blockade of mTOR by rapamycin efficiently boosted TLR-induced antigen-specific T and B cell responses to HBV and HCV vaccines. Taken together, these results reveal a novel mechanism through which mTOR regulates TLR-induced IL-12 and IL-10 production, contributing new insights for strategies to improve vaccine efficacy.
摘要：
The present study was to determine the targeting effect of M13 phage peptide ZL4 (MppZL4) on Schistosoma japonicum (S.j). Mice infected with S.j were injected with MppZL4. Real-time PCR was used to detect the distribution and metabolism of MppZL4 in the livers and lungs of mice. In vivo refusion test was performed to detect the targeting of MppZL4. Western blotting was employed to determine the expression of MppZL4. Live imaging was used to detect the distribution of oligopeptide MppZL4. Immunohistochemistry was employed to determine MppZL4 location on adult S.j body surface. Gomori method was employed to detect the influence of oligopeptide MppZL4 on alkaline phosphatase activity. The distribution and metabolism of MppZL4 and M13KE are not significantly different from each other at each time point. The abundance of MppZL4 is changed as S.j migrates in mice. The targeted binding effect of MppZL4 varies at different stages. ZL4 oligopeptide targets S.j in mice. The specific binding sites of MppZL4 on S.j body are mainly located in syncytial cells. The binding sites of MppZL4 on S.j body surface might be ALP or ALP-related proteins. MppZL4 had targeted binding effect on S.j with its binding site being associated with proteins related to S.j alkaline phosphatase. S.j tegument had a specifically binding site with exogenous peptides, offering new means to explore the interactions between hosts and parasites. Additionally, MppZL4 can possibly be used as targeting molecules in worm-resistant drugs or as tracing molecules in imaging diagnosis technologies.
