Essential genes of the macrophage response to Staphylococcus aureus exposure.

BACKGROUND: Although significant advances have been made in understanding the mechanisms of macrophage response to Staphylococcus aureus infection, the molecular details are still elusive. Identification of the essential genes and biological processes of macrophages that are specifically changed at different durations of S. aureus exposure is of great clinical significance. METHODS: We aimed to identify the significantly changed genes and biological processes of S. aureus-exposed macrophages. We systematically analyzed the macrophage gene expression profile GSE 13670 database with 8 h, 24 h or 48 h S. aureus infection. The results were further confirmed by western blot and quantitative polymerase chain reaction (qPCR) analyses. RESULTS: After 8 h of S. aureus infection, the expression of 624 genes was significantly changed. Six hundred thirteen differentially expressed genes (DEGs) were identified after 24 h of S. aureus infection. Two hundred fifty-three genes were significantly changed after 48 h of S. aureus infection. STAT1 was consistently up-regulated in these three treatments. TP53, JAK2, CEBPA, STAT3, MYC, CTNNB1 and PRKCA were only identified in the 8 h or 24 h S. aureus infection groups. CTNNB1 and PRKCA were for the first time identified as potential essential genes in S. aureus infection of macrophages. In the Gene Ontology (GO) term analysis, the defense response was shown to be the most significantly changed biological process among all processes; KEGG pathway analysis identified the JAK-STAT signaling pathway involved in early infection. CONCLUSIONS: Our systematic analysis identified unique gene expression profiles and specifically changed biological processes of the macrophage response to different S. aureus exposure times.

α­lipoic acid can greatly alleviate the toxic effect of AGES on SH­SY5Y cells.

The aim of the study was to explore the influence of α­lipoic acid (α­LA) on the cytotoxicity of advanced glycation end­products (AGEs) against SH­SY5Y cells. AGE­bovine serum albumin (BSA) was incubated in vitro using SH­SY5Y cells as a target model, and the control group was set. Cells were exposed to AGE­BSA, and α­LA was selectively added to the cells. Cell growth and death was determined by the MTT assay, which measures cellular metabolic rate, lactate dehydrogenase (LDH) leakage rate and cellular axonal length. Immunocytochemistry was employed to detect the expression of ß­amyloid (Aß) protein in cells, and mRNA expression of amyloid precursor protein (APP) and the receptor for AGE (RAGE) were assayed by PT­PCR. The metabolism of MTT was clearly increased, the rate of LDH leakage was significantly decreased, and axonal length was significantly increased in cells treated with α­LA (0.1 g/l) as compared to untreated cells. Furthermore, the expression levels of Aß protein were also decreased. In addition, α­LA (0.1 g/l) markedly inhibited the expression of RAGE mRNA, and did not influence APP mRNA expression as compared the control group. α­LA (0.1 g/l) was effective at dampening the cytotoxicity of AGE­BSA, a preliminary observation that confirms the ability of α­LA to significantly alleviate the cytotoxicity of AGEs against SH­SY5Y cells.

Associations of A-FABP with Anthropometric and Metabolic Indices and Inflammatory Cytokines in Obese Patients with Newly Diagnosed Type 2 Diabetes.

The study aimed to evaluate the relationship between anthropometric and metabolic indices, inflammatory cytokines, and adipocyte fatty acid-binding protein (A-FABP) in obese patients with newly diagnosed type 2 diabetes. The study included 48 nonobese subjects with newly diagnosed type 2 diabetes, 42 obese subjects with newly diagnosed type 2 diabetes, 30 simple obese subjects, and 30 matched normal subjects. Serum A-FABP was assessed by enzyme-linked immunosorbent assay. Pearson's correlations and multiple linear regression stepwise analysis were used to analyze correlations of A-FABP with anthropometric and metabolic indices and inflammatory cytokines. Obese subjects with newly diagnosed type 2 diabetes had elevated A-FABP compared to normal control, nondiabetic obese patients, and nonobese diabetic patients. A-FABP was significantly correlated with glycated hemoglobin A1C (HbA1C), BMI, triglyceride, Homeostasis Model Assessment Index (HOMA-IR), waist hip rate, C-reactive protein, IL-6, and HDL-C in obese subjects with type 2 diabetes. In multiple linear regression stepwise analysis, BMI, HbA1C, and HOMA-IR were significantly independent determinants for A-FABP. BMI, HbA1C, and HOMA-IR are independently associated with A-FABP in obese subjects with newly diagnosed type 2 diabetes. A-FABP may be related to insulin resistance and inflammation in type 2 diabetes and concomitant obesity.

Serum YKL-40 levels in gestational diabetes mellitus.

OBJECTIVE: Serum YKL-40 levels are elevated in patients with type 1 and 2 diabetes. However, the correlation between YKL-40 and gestational diabetes mellitus (GDM) remains unknown. The present study compared serum YKL-40 levels in pregnant women with GDM and those with normal glucose tolerance and evaluated the relationship between YKL-40 and insulin-resistant syndrome. METHODS: Thirty-five patients with GDM and 43 age-matched healthy pregnant women at 24-28 weeks of gestation were studied. In addition to anthropometric assessments, serum glucose, insulin, YKL-40, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein and glycated hemoglobin were measured in all subjects. All subjects underwent a 2-h 75-g oral glucose tolerance test (OGTT). Body mass index (BMI) and the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS: Fasting and 2 h serum YKL-40 levels were significantly higher in pregnant women with GDM compared with controls (77.3 ± 29.3 versus 50.9 ± 16.7 ng/mL, p < 0.001, fasting concentrations; 63.5 ± 20.1 versus 40.6 ± 10.7 ng/mL, p = 0.009, 2 h concentrations). OGTT had no effect on YKL-40 levels in either group (p > 0.05). There were significant correlations between YKL-40 and glycated hemoglobin (ß = 0.37, p = 0.006), fasting insulin (ß = 0.49, p = 0.001) and HOMA-IR (ß = 0.18, p = 0.015) in the GDM group. CONCLUSIONS: Serum YKL-40 levels are elevated in patients with GDM but are unaffected by OGTT. YKL-40 levels are related to glycated hemoglobin, fasting insulin and HOMA-IR. These results suggest that YKL-40 may be a major contributor to GDM.

Clinical and pathological analysis of 116 cases of adult adrenal cortical adenoma and literature review.

BACKGROUND: The aim of this study is to investigate origin, gross features, microscopic features, immunohistochemical properties, and differential diagnosis of adrenal cortical adenoma (ACA) in patients ≥20 years old. METHODS: The clinicopathological features of 116 cases of ACA and the immunohistochemical features of 50 cases of ACA were evaluated, and the relevant literature was reviewed. RESULTS: In our cohort, 76.72% (89/116) of the cases were functional, and 27 cases had non-functional, benign adrenal adenomas. ACA presented as an island tumor with an envelope, and the mean tumor size was 3.6 cm (range 1-5 cm), with a mean tumor weight of 9.28 g (range 5-113 g). The shape of the tumor cells was consistent, and mitosis was rarely observed. Forty of the 46 patients with cortisol-secreting ACA had tumors containing granule cells. Primary aldosteronism was observed in 43 cases. Thirty-eight cases had endoscopically visible tumors, with clear cells and lipid-rich cytoplasm arranged in irregular patches or strips. Cortisol-producing ACAs were associated with atrophy of the non-tumorous cortex. Adrenocortical adenomas displayed positive immunohistochemical staining for MELAN-A, Syn (46 of 50 cases of ACA), NSE (44 of 50 cases of ACA), Vim (42 of 50 cases of ACA) and Ki-67 <5% (24 of 50 cases of ACA; the remaining 26 cases were negative for Ki-67). CONCLUSION: Prediction of endocrine syndrome in functional ACA was possible based on its structure and morphologic features, which could prevent an unanticipated postoperative crisis. However, a clinical study is needed to validate these findings.

Relationship between adiponectin and testosterone in patients with type 2 diabetes.

INTRODUCTION: This study was designed to investigate the relationship between serum adiponectin and testosterone in patients with type 2 diabetes. MATERIALS AND METHODS: Serum level of adiponectin and testosterone were prospectively measured in 65 patients with type 2 diabetes and in 20 healthy subjects. Testosterone was determined by the radio-immunoassay whereas adiponectin levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The average serum testosterone did not differ between the diabetes and the control group, but the average adiponectin in the diabetes group was lower (14.6 (14.2-15.0) vs. 24.3 (24.05-24.55) ng/mL, P = 0.001). In the diabetes group, the serum adiponectin level in patients with renal dysfunction (22.3 (21.5-23.1) ng/mL) was higher than in patients with no complications (12.1 (11.45-12.75) ng/mL) and than in patients with coronary artery disease (11.2 (10.25-12.15) ng/mL) (P = 0.009). Univariate correlation analysis showed an inverse weak correlation between adiponectin and testosterone concentrations in male diabetic patients (r = -0.27, P = 0.009). There was no significant correlation between adiponectin and testosterone in female patients (r = -0.05, P = 0.167). CONCLUSIONS: We conclude that patients with type 2 diabetes have lower serum adiponectin concentration than healthy individuals, and that there is a weak inverse correlation between adiponectin and testosterone serum concentrations in male diabetics.

[Study on the change of myocardial cell and matrix in the rats with insulin resistance and type 2 diabetes mellitus].

OBJECTIVE: To explore the injury of insulin resistance on cardiac muscle cell and matrix, and the relationship between insulin resistance and diabetic cardiomyopathy. METHODS: Twenty four Wistar rats of 6 months were randomly divided into normal control (N), insulin resistance group (I), diabetic group (D). Euglycemic insulin clamp technique (EICT) was used to determine insulin resistance (IR). Cadiocyte apoptosis was evaluated by TUNEL. Heart weight (HW) and body weight (BW) were measured to calculate HW/BW. Ultra-microstructure of cardiac muscle cell and structure of heart was observed. Masson dyeing, hydroxyproline detection and immunohistochemistry were used to measure the levels of collagen protein. RESULTS: Compared with controls, GIR decreased remarkably in D group and I group (P < 0.01). The number of apoptosis cell in I group was lower than that of D group (P < 0.01), and higher than that of N group (P < 0.01). Injury change of ultramicrostructure of myocardial cell was observed in the rats with type 2 diabetes mellitus or insulin resistance. Interstitial fibrosis of heart occurred in D group and I group. Content of Hydroxyproline, the level of I , III type of collagen, and the total level of collagen in I group were lower than those in D group, and higher than those in N group (P < 0.05). CONCLUSION: Insulin resistance in the rats with type 2 diabetes mellitus or insulin resistance can injury myocardial cell and matrix.