Literature-based discovery of diabetes- and ROS-related targets

Abstract Background Reactive oxygen species (ROS) are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins) collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG) of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/). Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.http://deepblue.lib.umich.edu/bitstream/2027.42/78315/1/1755-8794-3-49.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/2/1755-8794-3-49-S7.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/3/1755-8794-3-49-S10.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/4/1755-8794-3-49-S8.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/5/1755-8794-3-49-S3.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/6/1755-8794-3-49-S1.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/7/1755-8794-3-49-S4.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/8/1755-8794-3-49-S2.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/9/1755-8794-3-49-S12.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/10/1755-8794-3-49-S11.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/11/1755-8794-3-49-S9.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/12/1755-8794-3-49-S5.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/13/1755-8794-3-49-S6.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/14/1755-8794-3-49.pdfPeer Reviewe

The effect of valsartan therapy on serum PAI-I levels of patients with metabolic syndrome

European Congress of Clinical Biochemistry and Laboratory Medicine (EUROMEDLAB 2005) -- MAY 08-12, 2005 -- Glasgow, SCOTLANDWOS: 000229250402089IFCC, FESC

Prolactin effect on blood glucose and insülin in breastfeeding women

PubMed ID: 31235091Introduction: Prolactin plays a significant role in lactation and prolactin levels are increasing physiologically in pregnancy and breastfeeding period. There might be different mechanisms during breastfeeding between prolactin and insülin levels. In order to highlighten this mechanisms we compared the plasma levels of glucose, insülin, prolactin, C-peptid in basal situations and after taking 75 gr carbonhydrate, 20 gr protein, 23 gr fat in breastfeeding and in non lactating women. Material and methods: Participiants and measurements: The study population included 12 breastfeeding women and 11 healthy non lactating women as a control group. We collected information on age, history of gestational diabetes mellitus, family history of diabetes mellitus, natality, the symptoms of hypoglycemia. Weight, height and waist circumference were measured and body mass index (BMI) was calculated as weight (kg)/height (m 2 ). Results: Prolactin was inversely correlated with HbA1c and 2. hour C peptide (p=0.005, r=-0.564; p=0.008, r=-0.539). Prolactin was not significantly correlated with HOMA-IR, HOMA-IS, AUC-I or AUC-G. Prolactin levels were higher in breastfeeding women (median:34.98 µg/L) than in non lactating women (median:12.21 µg/L, p<0.001). There was a significant association between age and fasting glucose (p=0.018, r=-0.665), 2. hour glucose (p=0.049, r=0.578) in breastfeeding women. Discussion: In our study, we displayed prolactin was inversely correlated with HbA1c and 2. hour C peptide. Some studies in the past demonstrated that higher prolactin levels had importantly lower prevelance of type 2 diabetes. Our findings supported this situation. © 2019 Diabetes Indi

The Relationship Between Blood Hypoxia-Inducible Factor-1?, Fetuin-A, Fibrinogen, Homocysteine, and Amputation Level

2-s2.0-85089994653Reduced life expectancy has resulted from an increased incidence of chronic complications in patients with diabetes. The diabetic foot is one of these complications and generally presents together with diabetic neuropathy and vascular insufficiency. Hypoxia-inducible factor-1? (HIF-1?) is important in developing the adaptation response to hypoxia and facilitates healing through regulation of keratinocyte migration and epithelium restoration in wounds. Fetuin-A is a transporter protein that is synthesized in the liver and inhibits vascular and ectopic calcifications. It has been observed that altered fetuin-A is associated with peripheral artery disease through vascular calcification and is associated with inflammation and metabolic syndrome occurrence in diabetic patients. Fibrinogen is an acute-phase reactant and has a major role in homeostasis, tissue repair, and wound healing. Increased fibrinogen blood level is one of the factors that facilitates the hypercoagulability in diabetics. Homocysteine has atherogenic features and causes vascular toxicity by enhancing low-density lipoprotein oxidation. We evaluated the association of serum HIF-1?, fetuin-A, fibrinogen, and homocysteine levels with amputation in 31 patients diagnosed with diabetes mellitus. According to our evaluation, a negative correlation was determined between fetuin-A and amputation level (P =.012, r = ?0.450), which was statistically significant. Unfortunately, there was no significant correlation between HIF-1?, fibrinogen, homocysteine, and amputation level (P >.05). As a result, it was suggested that vascular calcification due to fetuin-A deficiency may be important in the diabetic foot pathogenesis and that fetuin-A levels may be a predictor for amputation level. © The Author(s) 2020.16-TIP-011The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Ege University Scientific Research Project Commission (Project No. 16-TIP-011)

The effect of hormone replacement treatment on thrombin-activatable fibrinolysis inhibitor activity levels in patients with Hashimoto thyroiditis

PubMed ID: 19252348Background: Hypothyroid patients have increased risk of cardiovascular diseases, and several mechanisms have been considered responsible in these patients. Although, a few studies demonstrated fibrinolytic system changes in hypothyroid patients, there is no study demonstrating TAFI activity in hypothyroid Hashimoto's thyroiditis patients. The aim of this study was to evaluate TAFI activity status and the effect of L thyroxin hormone replacement treatment on fibrinolytic system in this patient group. Methods: Thirty patients with hypothyroid Hashimoto thyroiditis (all were female and the mean age was 44.3±14.6 years, ranging between 17-68 years) were enrolled to study. Their TSH levels were high (27.2±5.2 mU/L) and Free T3 and Free T4 hormone levels were below than normal. In this study, euthyroid 20 healthy volunteers (mean age 32.5±4.9 years, range 26-42 years) were adopted. L-thyroxin treatment before and after TAFI activity levels were measured in patients. Results: In the control group, TAFI activity levels were 9.6±0.4 µg/mL. In patients with L-thyroxin before and after treatment there were high levels of TAFI activity value of 14.2±0.9 and 12.9±0.8 µg/mL, respectively. In the patient group, after L-thyroxin treatment TAFI activity levels were decreased but they were not statistically significant (p=0.187). When compared to the control group, high levels of TAFI activity were observed in the patient group (p<0.0001). Conclusion: Our data demonstrated that in Hashimoto thyroiditis, patients have high levels of TAFI activity compared to controls. A high level of TAFI activity suggests fibrinolytic deficit or thrombotic tendency in hypothyroid patients and this deficit is persistent after L-thyroxine replacement. © 2009 The Japanese Society of Internal Medicine

Effect of enalapril on urinary glycosaminoglycan, heparan sulphate and microalbuminuria in type II diabetic patients

WOS: 000083179000004PubMed ID: 23902355Recent studies in diabetic humans have shown that angiotensin converting enzyme (ACE) inhibitors may provide additional renal benefit above and beyond conventional antihypertensive agents. We investigated the effect of enalapril on urinary glycosaminoglycans (GAG), heparan sulphate (HS) and microalbuminuria (MAU) in diabetic patients. Urinary GAG and HS levels were determined in controls (n = 16, 41.3 +/- 12.9 years old) and in type II diabetics (n = 18, 53 +/- 9.6 years old) who were not using ACE inhibitors. Four of these patients had also hypertension. The duration of diabetes was 5.5 +/- 3 years (mean +/- SD). Microalbuminuria was detected in seven patients. The subjects were treated with enalapril (5-10 mg day(-1)) for 6 weeks. The median values of GAG (n = 18, 2.8 mg uronic acid g(-1) crea. day(-1)) and HS (n =18, 1.36 mg glycosamine g(-1) crea. day(-1)) in the pre-treatment group were significantly (p < 0.01) higher than the control group (n = 16, 1.98 mg uronic acid g(-1) crea. day(-1) and 0.87 mg glycosamine g(-1) crea. day(-1)), respectively. Before treatment, GAG and HS levels seemed to be not different between microalbuminuric and normoalbuminuric as well as hypertensive and normotensive patients. Following enalapril treatment, the median values of GAG (n =18, 1.35 mg uronic acid g(-1) crea. day(-1)) and HS (n = 18, 0.99 mg glycosamine g(-1) crea. day(-1)) tended to decrease to the levels which were not significantly different from the control group. Following treatment, significant reduction in urinary albumin excretion (from 15.45 to 11.1 mg day(-1)) (p < 0.0005) was also observed. When considering the pre- and post-treatment concentrations, there were positive correlations between urinary GAG and HS values (p < 0.05, r = 0.6541 and p < 0.01, r = 0.5984). These results suggest that measurement of urinary heparan sulphate may be another useful predictor of clinical diabetic nephropathy; and enalapril causes marked reduction in HS and GAG values in all patients independently by the presence of hypertension