ABSTRACT
Microglia play a crucial role in the activation of immune defense mechanism as the resident macrophages in the central nervous system (CNS). Microglia can eliminate damaged neurons, plaques, and other infectious agents. Triggering receptor expressed on myeloid cell-2 (TREM-2) speculates to be beneficial in preventing inflammation-induced bystander damage of neurons. However, the precise molecular mechanisms underlying the regulation of TREM-2 on neurons are not clarified. We cultured PC12 cells with conditioned medium which was the supernatant of LPS-treated BV2 cells and six groups of PC12 cells (control group, LPS group, TREM-2 WT + LPS group, TREM-2 over-expression + LPS group, siRNA control + LPS group, and siRNA TREM-2 + LPS group) were investigated. The mRNA levels of inflammatory mediators: Nitric oxide synthase (iNOS) and Arginase-1(Arg-1) were quantified by using RT-PCR. Assessment of apoptosis in PC12 cells mediated by BV2 microglia was analyzed using TUNEL assays. The result showed that LPS stimulation significantly enhanced inducible iNOS (M1) production in BV2 cells (P < 0.01), and increased PC12 cells apoptosis (P < 0.01), while reduced the production of Arg-1 (M2) in BV2 cells (P < 0.01). These effects were attenuated by TREM-2 over-expression, but enhanced by TREM-2 silencing. It indicated that TREM-2 inhibited LPS-mediated neuronal apoptosis by down-regulating iNOS and up-regulating the expression of Arg-1 in BV2 microglia. Therefore, our findings may provide new insights in the regulation of TREM-2 on neuronal apoptosis via BV2 microglial M1/M2 modulation.
Subject(s)
Lipopolysaccharides , Microglia , Humans , Rats , Animals , PC12 Cells , Microglia/metabolism , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Macrophages , RNA, Small Interfering/metabolism , RNA, Small Interfering/pharmacologySubject(s)
Hypertrophy/metabolism , Hypertrophy/pathology , Ligamentum Flavum/metabolism , Ligamentum Flavum/pathology , Macrophage Migration-Inhibitory Factors/metabolism , Collagen Type I/metabolism , Collagen Type III/metabolism , Dinoprostone/metabolism , Extracellular Matrix/metabolism , Humans , Interleukin-1alpha/metabolism , Interleukin-6/metabolism , Lumbosacral Region , Matrix Metalloproteinase 13/metabolism , Nitric Oxide/metabolism , Spinal Canal/metabolism , Spinal Stenosis/metabolism , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To examine the associations between inflammatory markers, coagulation and fibrinolysis parameters, and microvascular complications in 182 Chinese patients with type 2 diabetes mellitus (T2DM) who sought treatment at a large hospital in Zhejiang province, China. METHODS: We investigated the relationships of blood inflammatory markers with hemostatic markers in 87 patients with T2DM who did not have complications and 95 patients with T2DM who had microvascular complications. RESULTS: C-reactive protein (CRP) and interleukin-6 (IL-6) were significantly correlated with fibrinogen, thrombin-antithrombin III complex (TAT III), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and coagulation factors (F) VII in patients with T2DM who had microvascular complications (P <.05). Based on logistic regression analysis, the highest-tertile groups of fibrinogen, FVII, and FVIII, corresponded to a greater risk of high CRP, whereas risk of high IL-6 was significantly greater in the groups with highest-tertile values for fibrinogen, FVII, TAT III, PAI-1, and activated protein C (APC). CONCLUSIONS: Elevated levels of CRP and IL-6 might be associated with increased coagulability and a tendency towards thrombus formation in patients with T2DM who have microvascular complications.
Subject(s)
C-Reactive Protein/metabolism , Diabetes Mellitus, Type 2/complications , Endothelium, Vascular/pathology , Interleukin-6/metabolism , Adult , Aged , Antithrombin III , Asian People , Factor VII , Female , Fibrinogen , Humans , Male , Middle Aged , Plasminogen Activator Inhibitor 1 , Regression Analysis , Statistics, Nonparametric , von Willebrand FactorABSTRACT
BACKGROUND: Serum sialic acid (SA) is an acute phase response marker. Additionally, it is an independent risk factor for atherosclerotic disease and is higher in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to determine the association of SA with blood coagulation and fibrinolysis in T2DM patients. METHODS: The levels of serum SA and blood coagulation and fibrinolysis markers were measured in patients with T2DM. The associations of SA with hemostatic markers and other variables were assessed. RESULTS: There were significant correlations between SA and fibrinogen, D-dimer, factor (F) IX, and platelet (PLT) that were independent of smoking, body mass index (BMI), waist-to-hip ratio, hemoglobin A(1c) (HbA1c), fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) ratio, and antithrombotic therapy history. Based on logistic regression analyses, the highest tertile groups of fibrinogen, D-dimer, F VIII, F IX, and PLT showed a significantly increased risk of high SA compared with the lowest tertiles after adjusting for age, gender, and antithrombotic therapy history. SA also significantly correlated with duration of diabetes, BMI, FPG, TG, low-density lipoprotein cholesterol (LDL-c), TC-to-HDL-C ratio, and albumin-to-creatinine ratio (ACR). CONCLUSIONS: Elevated serum SA levels are associated with increased coagulability and higher risk of thrombus formation in T2DM patients.
Subject(s)
Diabetes Mellitus, Type 2/blood , Fibrinolysis , N-Acetylneuraminic Acid/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Middle AgedABSTRACT
Lipid metabolic disturbances are related to many diseases, such as obesity, diabetes, and certain cancers. Notably, lipid metabolic disturbances have been reported to be a risk factor for colorectal cancer. Nuclear receptors act as ligand-dependent transcription regulators and play key roles in the regulation of body lipid metabolism and the development of many cancers. Retinoic acid receptor-related orphan receptor α (RORα) is a nuclear receptor and can regulate several lipid metabolism genes in certain cancers. Herein, we demonstrate that the conditioned medium from adipocytes has a proproliferative and promigratory effect on colorectal cancer cells and enhances angiogenesis in chicken embryonic chorioallantoic membranes. In addition, the conditioned medium leads to a decrease in the expression of RORα and its target genes. Meanwhile, RORα and its target gene expressions are lower in human colorectal tumor tissue compared with control colorectal tissue. Activation of RORα inhibits the effect of conditioned medium on the proliferation and migration of colorectal cancer cells as well as the angiogenesis in chicken embryonic allantoic membranes. In colorectal cancer cells, the putative ligand of RORα, cholesterol sulfate (CS), prevents cell cycle progression at the G1/S boundary and concurrently modulates the expression of cell cycle-regulatory genes in colorectal cancer cell. CS inhibits angiogenesis in chicken embryonic chorioallantoic membranes and concurrently decreases the mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α as well as the secretion of VEGF. In addition, lipogenic gene expression is higher in human colorectal tumor tissue compared with control colorectal tissue. CS inhibits the expression of lipogenic genes in colorectal cancer cells. These results suggest that RORα could represent a direct link between local lipid metabolism of colorectal tissue and colorectal cancer. Therefore, the reduction of the expression of RORα could represent a potential warning sign of colorectal cancer.
Subject(s)
Cell Movement/physiology , Cell Proliferation/physiology , Chorioallantoic Membrane/physiology , Colorectal Neoplasms/metabolism , Culture Media, Conditioned/pharmacology , Nuclear Receptor Subfamily 1, Group F, Member 1/biosynthesis , 3T3 Cells , Adipocytes/physiology , Animals , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell Survival/physiology , Chick Embryo , Chorioallantoic Membrane/blood supply , Chorioallantoic Membrane/drug effects , Colorectal Neoplasms/pathology , Humans , Mice , Neovascularization, Physiologic/drug effects , Neovascularization, Physiologic/physiology , Nuclear Receptor Subfamily 1, Group F, Member 1/antagonists & inhibitorsABSTRACT
OBJECTIVE: A systematical investigation on the distribution of wild germplasm of Regonia fimbristipula in Dinghu District, Zhaoqing City, Guangdong Province was conducted at 8 sites. METHODS: Field quadrat survey method was carried out. RESULTS: Begonia fimbristipula had obvious phenotypical plasticity showing three phenotypes with red, green and bicolor leaf, respectively. Its populations lived in the ecological environment of rock. The growth and building of Begonia fimbristipula population were mutually influenced by many ecological factors such as natural habitat, slope-exposure, soil thickness, sunlight, air humidity as well as soil physical and chemical properties. CONCLUSION: Living environment vulnerability and human activities are the main reason causing sharp decrease of wild resources of Begonia fimbristipula. Evaluation on regional distribution of wild Begonia fimbristipula and its protection and use of the rationalization have important value.
Subject(s)
Begoniaceae/growth & development , Begoniaceae/genetics , Conservation of Natural Resources , Ecosystem , Begoniaceae/classification , China , Ecology , Genetics, Population , Plants, Medicinal/genetics , Plants, Medicinal/growth & development , SoilABSTRACT
OBJECTIVE: To study the effect of different plant growth substance and activated charcoal on rooting in culture seedling of Begonia fimbristpula on Dinghushan mountain. METHODS: Tissue culture single factor experiment method was used. RESULTS: NAA 0. 3 mg/L + IBA 0. 2 mg/L preferably induction adventitious bud clump with corm to take rooting, but the number of adventitious root were less, short and small, callow shoot more germination. 300 mg/L activated carbon obviously increased radicate quality and inhibited fine buds point differentiation, root number up to 15.5 institia, root length range was 2.0-5.1 cm, root system developed. Tissue culture seedlings were higher, corn and leaf were good quality, strong growth. Took root of seedling cultivation with bulb for bush in the form of scattered bud planted to peat soil: perlite (3:1) mixed in matrix, after the transplant survival rate reached 100%, plant form seedlings fast, grew exuberant. CONCLUSION: MS with sucrose 30 g/L + NAA 0.3 mg/L + IBA 0.2 mg/L + activated carbon 300 mg/L + carrageenan 7.0 g/L as the tissue culture seedling of Begonia fimbristipula radicate system, is rapid propagation and preserve local unique plant in an effective way.