[Effects of silence information regulator 7 on proliferation and apoptosis of mouse renal podocytes under high glucose environment].

Objective: To investigate the effects and its mechanisms of silence information regulator 7(SIRT7)on mouse renal podocytes proliferation and apoptosis under high glucose environment. Methods: Mouse renal podocytes cultured with high glucose and treated with different methods were divided into the following groups:control group(Control),high glucose group(HG),high glucose+transfecting with SIRT7 overexpression vetor(pcDNA3.1-SIRT7) group(SIRT7 OE+HG),high glucose+transfecting with the negative control vetor(pcDNA3.1)group(SIRT7 OE-NC+HG),high glucose+transfecting with small interfering RNA-SIRT7 (siRNA-SIRT7) group (siRNA-SIRT7+HG), high glucose+ transfecting with siRNA-SIRT7 control group (siRNA-SIRT7-NC+ HG). Viability of proliferation was examined by CCK-8 method.Rate of apoptosis was detected by flow cytometry. The level of SIRT7 mRNA expression was measured by qRT-PCR. Western blot was performed to detect the protein expression of Nephrin and key factors of Wnt/ß-catenin signaling pathway. Results: The CCK-8 result showed that,compared with control group, the proliferative activity of mouse renal podocytes in HG group was decreased (P＜0.05). After transfected with SIRT7 overexpression vetor or small interfering RNA-SIRT7,compared to HG group,the cell proliferation activity was further decreased in siRNA-SIRT7 group(P＜0.05),but it was enhanced in SIRT7 OE+HG group (P＜0.05). The results of flow cytometry showed that compared with the control group, the apoptosis rate of cells in the HG group was increased (P＜0.05). Compared with the HG group, the apoptosis rate of cells in the siRNA SIRT7+HG group was increased significantly(P＜0.05), while that in the SIRT7 OE+HG group was decreased (P＜0.05). Compared with control group,the expressions of Nephrin, Wnt5a and ß-catenin were inhibited in HG group (P＜0.05). compared to HG group,siRNA-SIRT7 could down-regulate the expression levels of Nephrin, Wnt5a and ß-catenin in siRNA-SIRT7 group (P＜0.05), SIRT7 overexpression could up-regulate the expression levels of Nephrin, Wnt5a and ß-catenin in SIRT7 OE+HG group (P＜0.05). Conclusion: The findings suggest that high glucose environment is an important factor to inhibit the proliferation and induce apoptosis of mouse renal podocytes.Overexpression of SIRT7 can reverse the effects by activating Wnt/ß-catenin signaling pathway and up-regulating ß-catenin expression.

Approach to Cushing's syndrome in pregnancy: two cases of Cushing's syndrome in pregnancy and a review of the literature.

Cushing's syndrome (CS) rarely occurs during pregnancy. The primary aim of this article is to propose a therapeutic approach to CS in pregnancy. Here, we present two cases of CS in pregnancy and a literature review. This article proposes the early diagnostic points, especially the clinical approach to this medical condition, mainly for pregnant women without a previous diagnosis of CS. More importantly, we present therapeutic strategies for CS during pregnancy, especially glucocorticoid replacement for perioperative, postoperative, and perinatal periods in pregnant women with CS in order to minimize complications for both mother and fetus. At the same time, we also assess the anxiety status of patients. This article summarizes the approach to CS in pregnancy, not only with a physiological assessment but with a psychological assessment as well.

Adropin deficiency worsens HFD-induced metabolic defects.

The limited efficacy of current treatment methods and increased type 2 diabetes mellitus (T2DM) incidence constitute an incentive for investigating how metabolic homeostasis is maintained, to improve treatment efficacy and identify novel treatment methods. We analyzed a three-generation family of Chinese origin with the common feature of T2DM attacks and fatty pancreas (FP), alongside 19 unrelated patients with FP and 58 cases with T2DM for genetic variations in Enho, serum adropin, and relative Treg amounts. Functional studies with adropin knockout (AdrKO) in C57BL/6J mice were also performed. It showed serum adropin levels were significantly lower in FP and T2DM patients than in healthy subjects; relative Treg amounts were also significantly decreased in FP and T2DM patients, and positively associated with adropin (r=0.7220, P=0.0001). Sequencing revealed that the patients shared a Cys56Trp mutation in Enho. In vivo, adropin-deficiency was associated with increased severity of glucose homeostasis impairment and fat metabolism disorder. AdrKO mice exhibited reduced endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), impaired glycosphingolipid biosynthesis, adipocytes infiltrating, and loss of Treg, and developed FP and T2DM. Adropin-deficiency contributed to loss of Treg and the development of FP disease and T2DM.

Correlation of early postoperative blood glucose levels with postoperative complications, hospital costs, and length of hospital stay in patients with gastrointestinal malignancies.

Early postoperative hyperglycemia in non-diabetic patients is an important risk factor affecting postoperative complications and mortality. This study aimed at investigating the effects of early postoperative hyperglycemia on postoperative complications, hospital costs, and length of hospital stay in non-diabetic patients with gastrointestinal malignancies; data of 1,015 non-diabetic patients with gastrointestinal malignancies, who underwent surgical intervention between January 2010 and January 2012, were retrospectively evaluated. Records on fasting plasma glucose (FPG), liver function, and kidney function were collected before and one day after surgery. Correlation of early postoperative FPG levels with postoperative complications, hospital costs, and length of hospital stay was further assessed in non-diabetic patients with gastrointestinal malignancies. One day after surgery, FPG results were significantly increased compared to preoperative values. FPG levels greater than or equal to 9.13 mmol/L (or 164.34 mg/dL) were associated with significant increases in the incidence of postoperative complications, length of hospital stay, and hospital costs. An association is shown between FPG and postoperative hyperglycemia in non-diabetic patients undergoing surgery for gastrointestinal malignancies. Significant increases in postoperative complications among these patients suggest that measurement of early postoperative FPG levels is critical to identify patients with postoperative hyperglycemia.

[Effect of advanced glycosylation end products on oxidative stress and MCP-1 in human renal mesangial cells].

OBJECTIVE: To investigate the effects of advanced glycosylation end products (AGEs) modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs). METHODS: HRMCs were cultured in vitro with medium containing different doses of AGE-BSA or BSA (50,100, 200, 400 mg/L) for 48 hours, or with AGE-BSA (200 mg/L) for different times (12, 24, 48, 72 h). Immunocytochemistry assay was used to estimate the protein level of RAGE. The ROS in cells were measured by flow cytometry and the mRNA expression of MCP-1 were analyzed by semi-quantiative reverse transcription-polymerase chain reaction (RT-PCR) after treatment with AGE-BSA or BSA. RESULTS: The protein level of RAGE was upregulated in the HRMCs with AGE-BSA. The expression of ROS and MCP-1 significantly enhanced by incubation of AGE-BSA in a time- and dose-dependent manner. The effects of AGE-BSA-induced up-regulation of ROS and MCP-1 level was significantly blocked by neutralizing antibodies to RAGE, while the expression of ROS and MCP-1 stood nearly unchanged after cultured with huamn IgG. CONCLUSION: The expression of ROS and MCP-1 in HRMCs is induced by AGE-BSA through RAGE, which may have potential effects in the pathgenic mechanism of diabetic nephropathy.

Immunohistochemical identification of osteoclasts and multinucleated macrophages.

Osteoclasts are bone-resorbing multinuclear cells derived from hematopoietic stem cells which are specialised to carry out lacunar bone resorption. The immunophenotype of giant cell-containing bone lesions in a wide range of osteoclast-like giant cells was similarly assessed. Both multinucleated macrophages and osteoclasts were found to express CD68. Multinucleated macrophages, but not osteoclasts, expressed GrB and Ki67. CD13+/CD14+/CD68+/GrB-/Ki67-/CD56- all giant-cell lesions noted in giant cells of bone. Giant cells have an osteoclast phenotype in most giant cell-rich lesions of bone, which do not express the macrophage-associated antigens GrB and Ki67. Our results indicate that they are formed from osteoclast precursors of mononuclear phagocyte.

Comparison of a multiple daily insulin injection regimen (glargine or detemir once daily plus prandial insulin aspart) and continuous subcutaneous insulin infusion (aspart) in short-term intensive insulin therapy for poorly controlled type 2 diabetes patients.

Aims. To examine the potential differences between multiple daily injection (MDI) regimens based on new long-acting insulin analogues (glargine or detemir) plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII) in patients with poorly controlled type 2 diabetes. Methods. Patients (n = 119) with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes.

Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes.

AIM: To evaluate the correlation between nonalcoholic fatty liver disease (NAFLD) and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS: Data were obtained from 1217 inpatients with T2DM (757 females, 460 males; aged 63.39 ± 12.28 years). NAFLD was diagnosed by hepatic ultrasonography. Diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR) were diagnosed according to their respective criteria. The prevalence of NAFLD and the independent correlations of clinical characteristics with NAFLD were determined by cross-tabulation and logistic regression, respectively. RESULTS: Approximately 61% of inpatients with T2DM in Qingdao, China had NAFLD, which decreased significantly with increase in age and prolonged course of diabetes. The prevalence of NAFLD in patients presenting with DN, DPN and DR was 49.4%, 57.2% and 54.9%, respectively. These rates were significantly lower than those of patients without DN, DPN and DR (65.9%, 65.6% and 66.1%, respectively, P < 0.05). Participants with NAFLD had greater body weight, waist circumference (WC), body mass index (BMI), fasting blood glucose (FBG), hemoglobin A1c, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, blood pressure, as well as triglyceride (TG) levels and lower high-density lipoprotein (HDL) concentration than those without NAFLD (P < 0.05). NAFLD was positively correlated with BMI, WC, TG, FBG, diastolic blood pressure, and systolic blood pressure but negatively correlated with the duration of diabetes, DR, DPN, DN, and HDL. CONCLUSION: Despite the benign nature of NAFLD, efforts should be directed toward early diagnosis, intensive blood glucose and blood pressure control, and effective dyslipidemia correction.

Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons.

Adiponectin secreted from adipose tissues plays a role in the regulation of energy homeostasis, food intake, and reproduction in the hypothalamus. We have previously demonstrated that adiponectin significantly inhibited GNRH secretion from GT1-7 hypothalamic GNRH neuron cells. In this study, we further investigated the effect of adiponectin on hypothalamic KISS1 gene transcription, which is the upstream signal of GNRH. We found that globular adiponectin (gAd) or AICAR, an artificial AMPK activator, decreased KISS1 mRNA transcription and promoter activity. Conversely, inhibition of AMPK by Compound C or AMPKα1-SiRNA augmented KISS1 mRNA transcription and promoter activity. Additionally, gAd and AICAR decreased the translocation of specificity protein-1 (SP1) from cytoplasm to nucleus; however, Compound C and AMPKα1-siRNA played an inverse role. Our experiments in vivo demonstrated that the expression of Kiss1 mRNA was stimulated twofold in the Compound C-treated rats and decreased about 60-70% in gAd- or AICAR-treated rats compared with control group. The numbers of kisspeptin immunopositive neurons in the arcuate nucleus region of Sprague Dawley rats mimicked the same trend seen in Kiss1 mRNA levels in animal groups with different treatments. In conclusion, our results provide the first evidence that adiponectin reduces Kiss1 gene transcription in GT1-7 cells through activation of AMPK and subsequently decreased translocation of SP1.

The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats.

Metformin appears to be involved in altering energy expenditure and thermogenesis, and could affect hypothalamic feeding circuits. However, it is not clear whether metformin is able to cross the blood-brain barrier (BBB) to reach the hypothalamus and exert a direct effect on the central nervous system. Here we show the presence of metformin in cerebrospinal fluid (CSF) of diabetic rats administered orally with metformin which was confirmed by detecting the concentration of metformin with liquid chromatography-tandem mass spectrometry. Food intake of diabetic rats treated with metformin was reduced, and glucose homeostasis was gained. Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) was increased but phosphorylated AMP-activated kinase (AMPK) was similar in the hypothalamus of metformin-treated diabetic rats. Our findings suggest that metformin may cross BBB and play a central mechanism on regulation of food intake in the hypothalamus. The anorexic effect of metformin may be mediated by inhibition of NPY and AgRP gene expression through the STAT3 signaling pathway.

GnRH secretion is inhibited by adiponectin through activation of AMP-activated protein kinase and extracellular signal-regulated kinase.

Adipokines produced from adipose tissues participate in regulation of reproduction, energy homeostasis, food intake, and neuroendocrine function in the hypothalamus. We have previously reported that adiponectin significantly reduced GnRH secretion from GT1-7 hypothalamic GnRH neuron cells. In this study, we further investigated the inhibition of GnRH secretion by adiponectin in vivo and found that extracellular signal-regulated kinase (ERK) was inhibited and AMPK activated. Furthermore, we found that activated AMPK by adiponectin reduced ERK phosphorylation, which possibly impaired GnRH secretion in GT1-7 cells.

Globular adiponectin regulates energy homeostasis through AMP-activated protein kinase-acetyl-CoA carboxylase (AMPK/ACC) pathway in the hypothalamus.

Adiponectin is a newly researched adipokine which participates in the regulation of energy homeostasis. AMP-activated protein kinase (AMPK) represents an energy sensor that responds to hormone and nutrition status in vivo and exerts a regulatory effect in the hypothalamus and multiple peripheral tissues. We investigated the possible mechanisms involved in appetite regulation by adiponectin in vitro with GT1-7 cells, a mouse immortalized hypothalamic neuron. The results showed that adiponectin increased the phosphorylation of AMPK, activated AMPK phosphorylated and inactivated acetyl-CoA carboxylase (ACC), and subsequently increased expression of agouti-related peptide (AgRP) mRNA. Our results also indicated that adiponectin had no effect on signal transducer and activator of transcription (STAT3). Together these findings suggest that adiponectin regulated energy homeostasis through the AMPK/ACC pathway but not the JAK/STAT3 pathway in the hypothalamus.

Epidemiology and characteristics of acute poisoning treated at an emergency center.

BACKGROUND: Acute poisoning is frequently encountered at emergency department. This study was to investigate the epidemiology and characteristics of patients with acute poisoning who were treated at the Emergency Center, Fujian Provincial Hospital, China. METHODS: We retrospectively analyzed the gender, age, causes of poisoning, types of poisons, poisoning route, emergency diagnoses, outcomes, and prognoses of these patients. RESULTS: Altogether 2867 patients with acute poisoning were treated from January 2004 to December 2009. The ratio of male to female was 1:1.04, and their average age was 33.8 years. Of the 2867 patients, 76.39% were between 18 and 40 years old. The incidence of acute poisoning was as high as 11.33% in January each year. The incidence of poisoning was in a descending order: alcohol poisoning (54.55%), medication poisoning (25.95%), pesticide poisoning (5.65%), and drug poisoning (4.88%). Most (56.44%) of the patients with drug poisoning were under 25 years and their mean age was significantly lower than that of patients with medication poisoning or alcohol poisoning (P < 0.01). Approximately 69.54% of the patients were followed up after emergency treatment, 30.39% were hospitalized, and four patients died. CONCLUSIONS: Acute poisoning is largely alcohol poisoning and medication poisoning in a city. The emergency green channel "pre-hospital emergency care-emergency department-hospital treatment" can significantly improve the survival rate of patients with acute poisoning.

Globular adiponectin inhibits GnRH secretion from GT1-7 hypothalamic GnRH neurons by induction of hyperpolarization of membrane potential.

Reproduction is accurately regulated by metabolic states in mammals. Adiponectin regulates luteinizing hormone (LH) secretion in the pituitary and energy homeostasis in the hypothalamus. We further investigated the gonadotropin-releasing hormone (GnRH) secretion regulation by adiponectin and its related molecular and electrophysiological mechanisms. The results showed that adiponectin receptors (AdipR1 and 2) were expressed in GT1-7 cells derived from hypothalamus neurons. GnRH secretion was inhibited via activation of AMP-activated protein kinase (AMPK). Moreover, we revealed that hyperpolarization of plasma membrane potentials and reduction of calcium influx was also caused by adiponectin.

[Effects of captopril on myocardial tissue energy metabolism and inflammation in rats with diabetic cardiomyopathy].

OBJECTIVE: To study the protective mechanism of captopril in diabetic cardiomyopathy by means of DNA microarray. METHODS: Rat models of diabetic cardiomyopathy were divided into test and control groups (n=5), and the rats in the test group were given oral captopril (1.5 mg/kg b.w.) for 15 weeks. DNA microarray was prepared by blotting the PCR products of 4 000 rat cDNAs onto a specially treated glass slides. The probes were prepared by labeling the mRNA from the myocardial tissue of both control and test groups with Cy3-d UTP and Cy5-d UTP separately through reverse transcription. The arrays were then hybridized against the cDNA probes and the fluorescent signals scanned. RESULTS: The expression of genes in relation to fatty acid b oxidation, mitochondrial proton-electron coupling and oxidative phosphorylation, and that of dithiolethione-inducible gene-1 were up-regulated, while the dimethylarginine dimethylaminohydrolase gene expression was obviously lowered in the test group in comparison with those of the control group. CONCLUSION: Captopril may protect the myocardial tissue through improving myocardial energy supply and depressing inflammatory reaction.