Association between serum complement 1q and the associated factors of acute ischemic stroke in patients with type 2 diabetes.

OBJECTIVE: The aim of this study was to examine the association between serum complement 1q (C1q) and the associated factors of acute ischemic stroke in patients with type 2 diabetes (T2DM). METHODS: The baseline clinical variables of the participants were collected, and the levels of blood lipids, blood sugar, inflammatory cytokines, and C1q in the three groups were then compared. The variables which affected the associated factors of acute ischemic stroke in T2DM cases were determined. RESULTS: The levels of C1q in the DAIS group were increased significantly compared with those in the T2DM group. Receiver operating characteristic curve analyses showed that the AUC for C1q and the combined diagnosis of acute ischemic stroke were 0.830 (95%CI 0.747-0.914), with a sensitivity of 0.854 and specificity of 0.780. The results of Pearson's correlation analyses demonstrated that C1q was associated positively with low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (PBG), 2-h postprandial blood glucose (2h PG), and high-sensitive C reaction protein (hs-CRP) (all p < .05). Stratified analysis showed that there was a positive relationship between C1q and the associated factors of acute ischemic stroke for partial LDL-C, and hs-CRP strata. Logistic model analysis suggested that C1q was an independent risk factor for acute ischemic stroke in patients with T2DM. After adjusting for potential confounders, a one-standard deviation (SD) increase in C1q level was strongly related to an approximately 1.5-fold increased risk of acute ischemic stroke in cases with a hs-CRP ≥1.78 mg/L. CONCLUSION: In DAIS patients, the levels of C1q were increased significantly and were an independent associated factor which affected the occurrence of acute ischemic stroke.

MG53 represses high glucose-induced inflammation and angiogenesis in human retinal endothelial cells by repressing the EGR1/STAT3 axis.

BACKGROUND: Diabetic retinopathy (DR) is a vascular complication of diabetes mellitus that leads to visual injury and blindness. Both angiogenesis and inflammation play an important role in the pathogenesis of DR. Here we aimed to explore the mechanisms of mitsugumin 53 (MG53) in ameliorating the dysfunction induced by high glucose (HG) in humans retinal microvascular endothelial cells (HRECs). METHODS: HRECs were subjected to HG in the presence or absence of MG53 overexpression. The effect of MG53 on cell viability and inflammatory response in HG-treated HRECs was measured using the Cell Counting Kit-8 and ELISAs, respectively. Expression of MG53, EGR1, p-STAT3, FGF2, TGFB1, and Angiopoietin-1 in HG-treated HRECs was quantified by western blot or quantitative real-time polymerase chain reaction. RESULTS: HG significantly downregulated MG53 in HRECs, which reduced cell viability while inducing angiogenesis and inflammatory response. Upregulation of MG53 reversed these effects of HG. MG53 directly interacted with EGR1 and repressed its expression, which decreased phosphorylation of STAT3 and downregulated FGF2, TGFB1, and Angiopoietin-1. EGR1 up-regulation or STAT3 activation antagonized the protective effects of MG53. CONCLUSION: MG53 alleviates HG-induced dysfunction in HRECs by repressing EGR1/STAT3 signaling. Thereby MG53 may have therapeutic potential in DR.

Plasma progranulin concentrations are increased in patients with type 2 diabetes and obesity and correlated with insulin resistance.

Insulin resistance (IR) is considered to be one of the most important pathogenesis of glycolipid metabolism disorders. However, the molecular mechanism responsible for IR is not fully understood. Recently, the chronic inflammation has been proposed to be involved in the pathogenesis of IR. In this study, we aim to investigate the concentrations of plasma progranulin in Chinese patients with obesity (OB) and type 2 diabetes mellitus (T2DM), and its relationship to IR. Plasma progranulin concentrations were significantly higher in the T2DM patients than in the normal glucose tolerant (NGT) subjects (P < 0.01). Within the T2DM and the NGT patients, the concentrations of progranulin were significantly higher in obese subjects than that in the normal weight subjects (225.22 ± 34.39 ng/mL versus 195.59 ± 50.47 ng/mL and 183.79 ± 61.63 ng/mL versus 148.69 ± 55.27 ng/mL, P < 0.05). Plasma progranulin concentrations correlated positively with weight, waist circumferences, BMI, HbA1c, TG, IL-6, FINS and HOMA-IR (P < 0.05), while correlated negatively with HOMA- ß (P < 0.05). Multiple linear regression analysis showed that BMI, HbA1c, IL-6 and TG correlated independently with circulating progranulin concentrations (P < 0.05). These results suggested that Plasma progranulin concentrations were higher in Chinese patients with type 2 diabetes and obesity and correlated closely with glycolipid metabolism, chronic inflammation and IR.

Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance.

AIMS: To detect plasma secreted frizzled-related protein (SFRP) 5 levels in Chinese healthy, obese and type 2 diabetes mellitus (T2DM) subjects and to investigate the relationships between plasma SFRP5 levels and body fat parameters, insulin resistance, glucolipid metabolism and inflammation. METHODS: Eighty-nine subjects with normal glucose tolerance (NGT) and 87 subjects with T2DM were enrolled in this study. NGT and T2DM groups were divided into normal weight (NW) and obese (OB) subgroups separately. Anthropometric parameters such as body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) were examined. Plasma levels of SFRP5, IL-6, glucose, serum lipid, glycated hemoglobin (HbA1C) and fasting insulin (FINS) levels were measured. Insulin resistance index (IR) was assessed by homeostasis model assessment (HOMA). RESULTS: Plasma SFRP5 levels were lower in T2DM group than in NGT group. The levels of plasma SFRP5 in subjects with obesity were also lower than those in subjects with NW in both NGT and T2DM groups. T2DM-OB subgroup had lower plasma SFRP5 levels than that in NGT-OB subgroup. Plasma SFRP5 levels were negatively correlated with BMI, WC, WHR, fasting plasma glucose, HbA1C, triglyceride (TG), FINS, HOMA-IR and IL-6. Multiple stepwise regression analysis showed that HOMA-IR, BMI and TG were independently related with plasma SFRP5 levels. CONCLUSIONS: Plasma levels of SFRP5 were decreased in Chinese obese and T2DM subjects. SFRP5 was an independent factor affecting glucolipid metabolism, inflammation and IR. It may play an important role in the pathogenesis of obesity and T2DM.

The growth factor independence-1 (Gfi1) is overexpressed in chronic myelogenous leukemia.

The activation of ABL tyrosine kinase in BCR/ABL-positive chronic myelogenous leukemia (CML) leads to a diversity of biological changes related to the pathogenesis of the disease. In CML patients, we determined the expression of growth factor independence-1 (Gfi1), a transcription repressor with weak oncogenic activity. Our data demonstrated that the Gfi1 mRNA level in both the mononuclear cells and purified CD34(+) cells from CML were significantly higher as measured by quantitative real-time PCR. Using flow cytometry and Western blot, we also showed that the Gfi1 protein content was increased in CML CD34(+) cells. The expression of Gfi1 was correlated with BCR/ABL significantly. Gfi1 may be implicated in the pathogenesis of CML and can serve as a potential target for the management of the disease.

Changes of CD4+CD25+ regulatory T cells in patients with acute coronary syndrome and the effects of atorvastatin.

The function of CD4(+)CD25(+) regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-beta1 and IFN-gamma) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P<0.01), the inhibitory ability of Treg on the T lymphocytes proliferation was reduced (P<0.01), IFN-gamma levels were increased and IL-10 and TGF-beta1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-gamma was decreased significantly, while IL-10 and TGF-beta1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-beta1, but negatively with serum IFN-gamma and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.

[Establishment and application of a murine transplant model of bone marrow purging of metastatic breast cancer cells in vitro].

OBJECTIVE: To establish a murine transplant model for bone marrow purging of metastatic breast cancer and to explore the efficiency of Econazole (Ec) as a purging agent. METHODS: Mixtures of TSA /Neo breast cancer cells and murine bone marrow cells were transplanted into lethally irradiated mice following purging with Econazole or saline in vitro. The recipient mice were monitored for hematopoietic engraftment, appearance of metastatic nodules in lungs and the overall survival. RESULTS: All the mice receiving i.v. injection of TSA cells developed metastatic lung nodules. The hematological recovery was not delayed in mice transplanted with Ec purged bone marrow. More importantly, metastatic lung nodules were not seen in Ec treated group and the overall survival was improved. CONCLUSION: The purged metastatic breast cancer cell bone marrow transplant model was easily established and reproducible. Ec could be used to purge the bone marrow grafts contaminated with breast cancer cells.