Meta-analysis of the relationship between Dietary Inflammatory Index and esophageal cancer risk.

INTRODUCTION: Diet is closely related to the occurrence of esophageal cancer (EC). Dietary Inflammatory Index (DII), as a novel index that describes the inflammatory potential of diet, was widely used in many diseases. OBJECTIVE: To systematically analyze the relationship between DII and the risk of esophageal cancer. METHODS: We mainly searched relative studies in PubMed, Cochrane library, Web of Science, and other literature database. The random-effect model was used for meta-analysis, and subgroup analysis and sensitivity analysis were used to detect the origin of heterogeneity. RESULTS: We finally obtained 6 articles (8 studies). All studies were case-control studies which consisted of 1961 cases and 3577 controls. In this study, compared with the lowest DII category, the highest DII category had a higher risk of esophageal cancer, and the pooled odds ratio (OR) of the 8 studies were 2.54 (95% confidence interval (CI): 1.90-3.40; I = 65.7%, P = .005). Furthermore, regardless of the differences in published year, DII components, geographic location, and study quality, there was still an increased risk of esophageal cancer in the highest DII category compared with the lowest DII category. CONCLUSIONS: Our results inferred that DII was positively correlated with esophageal cancer risk and it could be used as a tool to predict the esophageal cancer risk and evaluate human health.

Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein.

Oxidized low-density lipoprotein (oxLDL)-regulated secretion of inflammatory cytokines in smooth muscle cells (SMCs) is regarded as an important step in the progression of atherosclerosis; however, its underlying mechanism remains unclear. This study investigated the role of toll-like receptor 4 (TLR4) in oxLDL-induced expression of inflammatory cytokines in SMCs both in vivo and in vitro. We found that the levels of TLR4, interleukin 1-ß (IL1-ß), tumor necrosis factor-α (TNFα), monocyte chemoattractant protein 1 (MCP-1) and matrix metalloproteinase-2 (MMP-2) expression were increased in the SMCs of atherosclerotic plaques in patients with femoral artery stenosis. In cultured primary arterial SMCs from wild type mice, oxLDL caused dose- and time-dependent increase in the expression levels of TLR4 and cytokines. These effects were significantly weakened in arterial SMCs derived from TLR4 knockout mice (TLR4-/-). Moreover, the secretion of inflammatory cytokines was blocked by TLR4-specific antibodies in primary SMCs. Ox-LDL induced activation of p38 and NFκB was also inhibited in TLR4-/- primary SMCs or when treated with TLR4-specific antibodies. These results demonstrated that TLR4 is a crucial mediator in oxLDL-induced inflammatory cytokine expression and secretion, and p38 and NFκB activation.

Two GH3 genes from longan are differentially regulated during fruit growth and development.

In the present work, two full length cDNAs of GH3 genes, named DlGH3.1 and DlGH3.2 were cloned from pericarp and aril tissues of the longan fruit, respectively. Three conserved motifs, SSGTSAGERK, YASSE and YRVGD, as a characteristic of the acyladenylate/thioester forming enzyme superfamily were observed in DlGH3.1 and DlGH3.2 proteins. DlGH3.1 mainly expressed in pericarp tissues while DlGH3.2 accumulated in both the pericarp and aril tissues during fruit growth and development. In addition, NAA treatment induced the expression of DlGH3.1 and DlGH3.2 in the pericarp tissues at 21 and 77days after anthesis (DAA), while only DlGH3.2 in the aril tissues could be induced by NAA at 77DAA. More importantly, ABA and ethrel treatments suppressed the accumulations of DlGH3.1 and DlGH3.2 in the pericarp tissues of longan fruit at 21DAA (a rapid growth stage of pericarp), but enhanced DlGH3.2 expression in the aril tissues at 77DAA (a fruit ripening stage). Furthermore, the expression patterns of DlGH3.1 and DlGH3.2 showed different tissue specificity. Thus, our results suggest that DlGH3.1 gene expression might be associated with pericarp growth, while DlGH3.2 accumulation is likely to be related to both pericarp growth and fruit ripening, and the responses of DlGH3s to plant growth hormones are different and dependent on fruit development stage and fruit tissue.

Genetic polymorphisms in chitinase 3-like 1 (CHI3L1) are associated with circulating YKL-40 levels, but not with angiographic coronary artery disease in a Chinese population.

BACKGROUND: We sought to examine if polymorphisms in the promoter region of YKL-40 gene (CHI3L1) are associated with serum YKL-40 levels and coronary artery disease (CAD) in Chinese patients. METHODS: Three single nucleotide polymorphisms (SNPs) (-329G>A, rs10399931; -247C>T, rs10399805; -131G>C, rs4950928) in the CHI3L1 promoter were determined in 213 consecutive patients with angiographically documented CAD (luminal diameter stenosis ≥50%) and 248 normal controls. Coronary cumulative obstruction score and number of diseased vessels represent the severity of CAD. Serum YKL-40 levels were assessed using an ELISA kit. RESULTS: Patients with CAD had remarkably higher serum YKL-40 levels compared to controls (p<0.001). There was no difference in the allele, genotype and haplotype distribution of these three SNPs between controls and CAD patients. The minor alleles of CHI3L1-329G>A and -131G>C were significantly associated with decreased serum YKL-40 levels in both controls (p = 0.001 and p<0.001, respectively) and CAD patients (p = 0.007 and p<0.001, respectively), whereas CHI3L1-247C>T had no appreciable effect. None of these genetic variants and haplotypes was associated with severity of angiographic CAD. CONCLUSIONS: CHI3L1-329G>A and -131G>C polymorphisms are associated with serum YKL-40 levels, but not with the prevalence or severity of CAD.

Increased serum YKL-40 and C-reactive protein levels are associated with angiographic lesion progression in patients with coronary artery disease.

OBJECTIVE: YKL-40 is a pro-inflammatory protein highly expressed in atherosclerotic plaques, and is related to prognosis of patients with coronary artery disease (CAD). This study aimed to assess the possible association between YKL-40 and coronary lesion progression in CAD patients. METHODS: A total of 313 patients with CAD, who underwent percutaneous coronary intervention (PCI) and follow-up angiography (mean 13.2+/-3.2 months) were recruited. Serum YKL-40 and high-sensitivity C-reactive protein (hsCRP) levels were measured using ELISA kits. RESULTS: Baseline serum YKL-40 and hsCRP levels were higher in those with lesion progression (all p<0.001 vs. patients without lesion progression), and correlated significantly with change of lumen diameter stenosis and cumulative coronary obstruction score (all p<0.01). Multivariable logistic regression analysis revealed that after adjusting for conventional risk factors, number of total coronary artery lesions, YKL-40 and hsCRP levels were independent determinants of lesion progression. An area under the curve of YKL-40 and hsCRP was 0.744 (CI 95% 0.685-0.804, p<0.001) and 0.716 (CI 95% 0.657-0.776, p<0.001), respectively. The optimal values of cut-off point were 74.98 ng/ml (sensitivity 70%, specificity 71%) for YKL-40 and 3.21 mg/l (sensitivity 66%, specificity 68%) for hsCRP to predict lesion progression. CONCLUSION: Increased serum YKL-40 and hsCRP levels are independently associated with lesion progression in patients with CAD.

Decreased serum esRAGE level is associated with angiographically determined coronary plaque progression in diabetic patients.

OBJECTIVE: This study evaluated the relationship between serum levels of endogenous secretory receptor for advanced glycation endproducts (esRAGE) and coronary plaque progression in diabetic and nondiabetic patients. DESIGN AND METHODS: Serum esRAGE level was measured and quantitative coronary angiography (QCA) was performed in 265 consecutive patients at baseline and 1-year follow-up. RESULTS: Comparing to baseline, serum esRAGE level was significantly increased during follow-up in nondiabetic patients without plaque progression (p=0.014), unchanged in nondiabetic patients with plaque progression and diabetic patients without plaque progression, and decreased in diabetic patients with plaque progression (p=0.011). Moreover, change of esRAGE levels correlated with change of QCA measurements. Multivariable regression analyses revealed that high-density lipoprotein cholesterol (OR=0.214, p=0.037), hypertension (OR=2.755, p=0.011), high-sensitivity C-reactive protein (OR=1.083, p<0.001) and change of esRAGE (OR=23.477, p<0.001) were independent risk factors for plaque progression in diabetic patients. CONCLUSIONS: This study demonstrated an association of decreased serum esRAGE level with coronary plaque progression in patients with diabetes.

Increased serum glycated albumin level is associated with the presence and severity of coronary artery disease in type 2 diabetic patients.

BACKGROUND: Glycated albumin is the predominant circulating Amadori-type glycated protein in vivo and plays a major role in the development of diabetic vascular complications. The aim of this study was to assess the relationship between increased serum glycated albumin level and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: In a total of 320 consecutive patients with T2DM, coronary angiography revealed normal coronary arteries in 83 patients (control group) and significant coronary stenosis (> or = 70% luminal diameter narrowing) in 237, of whom 51 patients had 1-vessel disease (Group I), 80 had 2-vessel disease (Group II), and 106 had 3-vessel disease (Group III). Serum glycated albumin, hemoglobin A(1c) (HbA(1c)) and tumor necrosis factor (TNF)-alpha levels, lipid profile, and renal function were measured. Logistic regression analysis was performed to determine the relative risk of serum glycated albumin level for the presence and severity of CAD. Multivariate stepwise linear regression analysis was done to identify independent determinants of the glycated albumin level. Serum glycated albumin (21.2+/-5.3% vs 19.4+/-4.3%, p=0.005) and TNF-alpha levels (123 +/-115 pg/ml vs 65+/-59 pg/ml, p<0.001) were significantly higher in patients with CAD than in controls, but serum HbAlc level did not significantly differ between them (7.6+/-1.3% vs 7.4+/-1.2%, p=0.19). There was a significant difference in serum glycated albumin level between Groups I and III (19.5+/-3.3% vs 21.8+/-5.7%, p<0.001). The serum glycated albumin level correlated with the number of diseased arteries (Spearman r=0.205, p<0.001), and was closely related to serum levels on admission of glucose (r=0.495, p<0.001), TNF-alpha (r=0.123, p=0.028), blood urea nitrogen (r=0.167, p=0.004), triglycerides (r=0.129, p=0.021), and HbA(1c) (r=0.795, p<0.001). Multivariate analysis indicated that serum levels of glucose (p<0.0001), TNF-alpha (p=0.001), blood urea nitrogen (p=0.004) and triglycerides (p=0.035) were independent determinants for glycated albumin. Logistic regression analysis revealed that glycated albumin > or = 19% (odds ratio (OR) 2.9, p<0.001) was an independent predictor for CAD and glycated albumin > or = 21% (OR 2.3, p=0.032) for 3-vessel disease prediction. The area under the receiver-operating characteristic curve for glycated albumin (0.620, 95% confidence interval (CI) 0.548 to 0.691, p=0.001) was superior to that for HbA(1c) (0.543, 95% CI 0.473 to 0.613, p=0.243). CONCLUSIONS: An increased serum level of glycated albumin is associated with the presence and severity of CAD, and may be useful in screening patients with T2DM.

Association of serum levels of glycated albumin, C-reactive protein and tumor necrosis factor-alpha with the severity of coronary artery disease and renal impairment in patients with type 2 diabetes mellitus.

OBJECTIVES: This study aimed to determine whether elevated serum levels of glycated albumin, high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-alpha were related to an increased risk for coronary artery disease (CAD) and renal insufficiency in patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Serum levels of glycated albumin, hsCRP, TNF-alpha and blood glycosylated hemoglobin A1c (HbA1c) were measured in 317 consecutive patients with T2DM and 309 normal controls. Patients with T2DM were grouped based upon coronary angiographic findings (Group I: 151 patients with normal coronary arteries; Group II: 166 patients with significant coronary stenosis [>70% luminal diameter narrowing]) and renal functional status evaluated by estimated creatinine clearance (CrCl) (normal renal function group: 187 patients with CrCl >90 mL/min; mild renal insufficiency group: 103 patients with CrCl 60-90 mL/min; moderate renal insufficiency group: 27 patients with CrCl 30-60 mL/min). Multivariate analysis was performed to determine independent risk factors for CAD and renal insufficiency in patients with T2DM. RESULTS: Serum levels of glycated albumin, hsCRP and TNF-alpha were significantly higher in Group II than in controls (P<0.01) and Group I (P<0.01). A significant difference was found in glycated albumin, hsCRP and TNF-alpha levels among diabetic patients with mild, moderate renal insufficiency and normal renal function (P<0.05). These biochemical measurements correlated significantly with number of diseased coronary vessels (P<0.01) and status of renal function (P<0.05). No difference existed in HbA1c levels between Group II and Group I, and among patients with various CrCL stages. Multivariate analysis revealed that male gender, old age and serum levels of glycated albumin, hsCRP, TNF-alpha and lipoprotein (a) were independent risk factors for CAD, and older age, hypertension and glycated albumin were for CrCl <60 mL/min in diabetes. CONCLUSIONS: Increased serum levels of glycated albumin, hsCRP and TNF-alpha are associated with the presence and severity of CAD and renal impairment in patients with T2DM.

Elevation of tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 levels in aortic intima of Chinese Guizhou minipigs with streptozotocin-induced diabetes.

BACKGROUND: Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). METHODS: Twenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet beta cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: Significant elevation in serum glucose levels was observed one month and six months after STZ induction (P < 0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet beta cells, while in pancreas of diabetic minipigs islet beta cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-alpha level in aotic intima conditioned medium, and significant elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR. CONCLUSIONS: The present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) significantly elevated in aortic intima of diabetic minipigs.

Value of serum glycated albumin and high-sensitivity C-reactive protein levels in the prediction of presence of coronary artery disease in patients with type 2 diabetes.

BACKGROUND: Coronary artery disease (CAD) is a major vascular complication of diabetes mellitus and reveals high mortality. Up to 30% of diabetic patients with myocardial ischemia remain asymptomatic and are associated with worse prognosis compared to non-diabetic counterpart, which warrants routine screening for CAD in diabetic population. The purpose of this study was to evaluate the clinical value of serum glycated albumin and high-sensitivity C-reactive protein (hs-CRP) levels in predicting the presence of CAD in patients with type 2 diabetes. METHODS: Three hundred and twenty-four patients with type 2 diabetes were divided into two groups based on presence (CAD group, n = 241) or absence (control group, n = 83) of angiographically-documented CAD (lumen diameter narrowing > or =70%). Serum levels of glycated albumin and hs-CRP as well as serum concentrations of glucose, lipids, creatinine, blood urea nitrogen and uric acid were measured in both groups. Predictors of CAD were determined using multivariate logistic regression model and receiver-operating characteristic (ROC) curves. RESULTS: Serum glycated albumin and hs-CRP levels were significantly increased in diabetic patients with CAD. Multivariate regression analysis revealed that male gender, age, serum levels of glycated albumin, hs-CRP, creatinine and lipoprotein (a) were independent predictors for CAD. Areas under the curve of glycated albumin and hs-CRP and for regression model were 0.654 (95%CI 0.579-0.730, P < 0.001), 0.721 (95%CI 0.658-0.785, P < 0.001) and 0.824 (95% CI 0.768-0.879, P < 0.001), respectively. The optimal values of cut-off point were 18.7% (sensitivity 67.9%, specificity 60.0%) for glycated albumin and 5.2 mg/l (sensitivity 72.2%, specificity 60.0%) for hs-CRP to predict CAD. Logistic regression model was defined as: P/(1-P) = EXP(-1.5 + 1.265 gender + 0.812 age + 1.24 glycated albumin + 0.953 hs-CRP + 0.902 lipoprotein(a) + 1.918 creatinine). The optimal probability value for predicting CAD in type 2 diabetic patients was 0.648 (sensitivity 82.3%, specificity 68.6%). CONCLUSION: Serum glycated albumin and hs-CRP levels were significantly elevated in patients with type 2 diabetes and CAD. The logistic regression model incorporating with glycated albumin, hs-CRP and other major risk factors of atherosclerosis may be useful for screening CAD in patients with type 2 diabetes.