Serum miRNA-499 and miRNA-210: A potential role in early diagnosis of acute coronary syndrome.

In clinical practice, there is still a need for novel biomarkers, which can reliably rule in or rule out acute coronary syndrome (ACS) immediately on admission. This is of particular interest in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) in whom diagnostic uncertainty is high. The aim of the present study is to evaluate the potential role of miRNA-499 and miRNA-210 as novel molecular biomarkers for early diagnosis of UA and NSTEMI suspected patients presented at the emergency unit. A total of 110 patients presenting to the intensive care unit (ICU) within 24 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 37 UA, 48 NSTEMI and 25 noncardiac chest pain (NCCP) patients. Immediately at enrollment, blood samples were taken for estimation of serum miRNA-499 and miRNA-210 expression levels by real time PCR. miRNA-499 and miRNA-210 expression levels were significantly increased in UA and NSTEMI patients compared with NCCP patients (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that the area under curve (AUC) of miR-499 for the diagnosis of UA and NSTEMI was 0.98 and 0.97, respectively; while the AUC of miRNA-210 was 0.84 and 0.90, respectively. The important finding of our study was that the AUC of miRNA-499 for the diagnosis of ACS patients with symptoms onset <3 h was 0.89, while the AUC of miRNA-210 was 0.86. Interestingly, combining miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.96, P < 0.001. In conclusion, serum miRNA-499 and miRNA-210 are associated with UA and NSTEMI and with those presenting within 3 h of symptom onset. Both miRNAs might be potentially novel biomarkers for accelerating the diagnosis of ACS patients in emergency unit. © 2016 IUBMB Life, 68(8):673-682, 2016.

Circulating serum irisin levels in obesity and type 2 diabetes mellitus.

Irisin is an exercise-regulated myokine inducing browning of white adipose tissue and has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes mellitus (T2DM). The aim of this study is to evaluate the circulating serum irisin levels in obesity and T2DM and also to elucidate possible relationships between serum irisin levels with anthropometric and metabolic parameters of obesity and T2DM. One hundred fifty newly diagnosed T2DM patients as well as 150 nondiabetic control subjects were enrolled in this study. Nondiabetic controls were then stratified according to their body mass index (BMI) into three subgroups; lean, overweight, and obese. Serum irisin levels were evaluated by enzyme-linked immunosorbent assay. Serum irisin levels were significantly decreased in T2DM patients compared with nondiabetic controls. Obese nondiabetic controls had significantly higher serum irisin levels compared with lean nondiabetic controls. In both nondiabetic controls and T2DM patients, serum irisin was significantly positively correlated with BMI (r = 0.985, P < 0.001 and r = 0.218, P = 0.007, respectively), fat mass (r = 0.959, P < 0.001 and r = 0.202, P = 0.013, respectively), fat-free mass (r = 0.606, P < 0.001 and r = 0.194, P = 0.017, respectively), fat-free mass index (r = 0.820, P < 0.001 and r = 0.179, P = 0.028, respectively), waist-to-hip ratio (r = 0.880, P < 0.001 and r = 0.194, P = 0.017, respectively), fasting insulin (r = 0.989, P < 0.001 and r = 0.207, P = 0.011, respectively), and HOMA-IR (r = 0.989, P < 0.001 and r = 0.185, P = 0.023, respectively), whereas; significantly negatively correlated with insulin sensitivity (r = -0.992, P < 0.001 and r = -0.187, P = 0.022, respectively). In this study, we demonstrated that circulating serum irisin levels were increased in obese nondiabetic subjects, while decreased in T2DM patients. Moreover, serum irisin levels were correlated with anthropometric and metabolic markers of obesity and T2DM. © 2016 IUBMB Life, 68(7):544-556, 2016.

Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus.

Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes and, unless arrested, leads to end-stage renal disease. Therefore, early prediction and detection of DN would greatly benefit the disease management and delay its progression. The aim of this study is to evaluate the levels of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary vitamin D-binding protein (uVDBP) in type 2 diabetic patients with different degrees of diabetic nephropathy (DN) and to assess the value of uMCP-1 and uVDBP in the early detection of DN. Seventy-five type 2 diabetic patients with normoalbuminuria (n = 25), microalbuminuria (n = 25), macroalbuminuria (n = 25), and 25 healthy controls were included in this study. Urinary MCP-1 and VDBP levels were evaluated by enzyme-linked immunosorbent assay. A significant elevation in the uMCP-1 and uVDBP levels was found in macroalbuminuric (p < 0.001) and microalbuminuric (p < 0.01) diabetic patients compared to that in normoalbuminuric diabetic patients and control subjects (p < 0.001). Correlation study revealed that both uMCP-1 and uVDBP were significantly positively correlated to urinary albumin/creatinine ratio (r = 0.968, p < 0.001 and r = 0.973, p < 0.001, respectively), serum urea (r = 0.461, p = 0.001 and r = 0.456, p = 0.002, respectively), and serum creatinine (r = 0.475, p = 0.001 and r = 0.448, p = 0.004, respectively) and significantly inversely correlated to glomerular filtration rate (r = -0.983, p < 0.001 and r = -0.988, p < 0.001, respectively). Receiver operating characteristic (ROC) curve analysis of uMCP-1 and uVDBP levels for early diagnosis and detection of DN revealed that the cut-off value of uMCP-1 was 110 pg/mg with 92% sensitivity and 100% specificity; whereas, the cut-off value of uVDBP was 550 ng/mg with 96% sensitivity and 84% specificity. The findings of the present study suggest that uMCP-1 and uVDBP may be considered as novel potential diagnostic biomarkers for the early detection of diabetic nephropathy.

Association of estrogen receptor ß and estrogen-related receptor α gene polymorphisms with bone mineral density in postmenopausal women.

The aim of the study was to investigate the possible association of AluI and RsaI polymorphisms of estrogen receptor ß (ER-ß) gene and 23-bp nucleotide repeat polymorphism of estrogen-related receptor α (ERRα) gene with bone mineral density (BMD) in postmenopausal Egyptian women. Two-hundred postmenopausal osteoporotic women as cases and 180 healthy age-matched postmenopausal women as controls were genotyped by PCR fragment length polymorphism for AluI, allele-specific PCR for RsaI, and by sizing of PCR products on agarose gels for ERRα repeats. sRANKL levels were estimated by ELISA. BMD measurements for spine and femoral neck were performed by dual energy X-ray absorptiometry. A significant difference between women with osteoporosis and controls regarding allele and genotype distributions of AluI G/A (OR 2.37, 95 % CI 1.77-3.18 and p < 0.001 for A allele) and ERRα polymorphisms (for the two repeats allele OR 2.08, 95 % CI 1.09-4.00, and p = 0.02). Osteoporotic women with the AluI AA + GA genotype or with the EERα 2,2 genotype had significantly lower BMD than did women with the other genotypes. Moreover, there was a significant increase of the mean values of sRANKL in carriers of AluI A, RsaI A alleles and in patients having 2,2 genotypes of ERRα (p < 0.001, p < 0.001, p = 0.02, respectively). We demonstrated an association of ER-ß AluI G/A and ERRα 23-repeats polymorphisms with BMD in postmenopausal Egyptian women. A possible effect of ER-ß and ERRα polymorphisms on the levels of sRANKL was estimated.

Association of adiponectin with cardiovascular events in diabetic and non-diabetic hemodialysis patients.

Adiponectin is a novel collagen-like protein synthesized by white adipose tissue. Its levels are decreased in obesity, type-2 diabetes and insulin-resistant states, and are increased in chronic renal failure. It has anti-inflammatory and anti-atherogenic properties. This study was planned to evaluate the levels of adiponectin in uremic patients with and without diabetes and to find any relationship between adiponectin levels and some cardiovascular risk factors, and to determine the possible predictive value of adiponectin for cardiovascular complications (CVC). The study included 100 subjects, 20 of them were healthy subjects and served as the control group (group I), 40 were uremic non-diabetic patients (group II) (half of them were without CVC, group IIA, and the other half were patients with CVC, group IIB) and, lastly, 40 uremic diabetic patients (group III) (half of them were without CVC, group IIIA, and the other half were patients with CVC, group IIIB). All subjects were subjected to complete clinical examination, including determination of mean arterial blood pressure (MABP), body mass index (BMI), waist to hip ratio, routine laboratory investigations, fasting plasma glucose, fasting plasma insulin, lipid profile (cholesterol, TG, LDL, HDL), determination of insulin resistance by homeostasis model assessment index (HOMA-IR) and estimation of serum levels of adiponectin. There was a significant increase in serum adiponectin levels in all the uremic patients (group II and group III) when compared with the control (group I) group, P <0.01; also, serum adiponectin levels were significantly decreased in uremic diabetic patients (group III) when compared with uremic non-diabetic patients (group II), P <0.01; but this was still higher than in the controls. The patients with CVC, whether uremic non-diabetic (group IIB) or uremic diabetic (group IIIB), had a significant decrease in serum adiponectin levels when compared with patients without CVC (group IIA and group IIIA), P <0.01. Serum adiponectin has a significant positive correlation with HDL and a significant negative correlation with MABP, BMI, plasma insulin, HOMA-IR, LDL, TG and cholesterol in all the patients. Therefore, it can be concluded that adiponectin levels in uremic patients, whether diabetic or non-diabetic, may be a good indicator of cardiovascular disease risk.

Endothelial nitric oxide synthase gene polymorphisms and the risk of diabetic nephropathy in type 2 diabetes mellitus.

Endothelial dysfunction plays an important role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy (DN). Endothelial nitric oxide synthase (eNOS) gene polymorphisms that affect eNOS activity are associated with endothelial dysfunction. The aim of this study was to evaluate the association of three polymorphisms of the eNOS gene (894G>T, -786T>C, and 27-bp-VNTR) with the risk of DN among type 2 diabetic patients. A total of 400 type 2 diabetic patients were enrolled in this study. The DN group comprised 200 patients; the group of diabetics without nephropathy comprised another 200 patients. Genetic analysis for eNOS gene polymorphisms was done in all subjects. Measurement of nitric oxide levels was estimated. The C allele for -786T>C and the T allele for 894G>T were significantly more frequent in diabetics with nephropathy than in diabetics without nephropathy (p<0.001; odds ratio [OR] and 95% confidence interval [CI] for the C allele=1.64 [1.24-2.17] and p<0.001; OR and 95% CI=1.7 [1.27-2.26] for the T allele). The haplotypes CTa (with all the mutant alleles) and CTb were significantly more common in patients with DN (p=0.01 and 0.003, respectively). These results suggested that the eNOS polymorphisms might represent genetic determinants for developing DN in type 2 diabetic Egyptians.

Mean platelet volume and its relation to insulin resistance in non-diabetic patients with slow coronary flow.

BACKGROUND: Increased mean platelet volume is a central process in the pathophysiology of coronary heart disease. Insulin resistance contributes to increased platelet activation. AIM: To assess the mean platelet volume and its possible relationship with insulin resistance in non-diabetic patients with slow coronary flow. METHODS AND SUBJECTS: The study included 60 patients with slow coronary flow and 20 subjects (controls) with normal coronary arteries. Slow coronary flow patients were divided into 2 groups, insulin resistant (32 patients) and insulin sensitive (28 patients) according to the homeostasis model assessment of insulin resistance index (HOMA-IR). RESULTS: Patients with slow coronary flow had significantly higher mean platelet volume values (7.9±0.47 vs. 7.1±0.5, p<0.01), insulin level (10.8±3.2 vs. 8.2±1.4, p<0.01), and HOMA-IR scores (2.72±0.85 vs. 1.84±0.19, p<0.01). These parameters were significantly higher in insulin-resistant patients than in insulin-sensitive ones. The mean platelet volume was correlated with HOMA-IR (r=0.52, p<0.01) and insulin level (r=0.58, p<0.01). In multivariate analysis, mean platelet volume and HOMA-IR were independent predictors of mean TIMI frame count {(B±SE=0.562±2.95, p<0.01) and (B±SE=0.538±2.46, p<0.01), respectively}. CONCLUSION: Patients with slow coronary flow have increased mean platelet volume which was associated with insulin resistance in non-diabetic slow coronary flow patients. TIMI frame counts correlated with mean platelet volume and increased insulin resistance. Thus, insulin resistance and platelet activity may have a role in the pathogenesis of slow coronary flow. Also, they may have a possible benefit as follow-up markers in non-diabetic patients with slow coronary flow.

Surgery for hemoptysis in various pulmonary tuberculous lesions: a prospective study.

Hemoptysis due to pulmonary tuberculous lesions is a common cause of morbidity, and occasionally mortality. The aim of this study is to evaluate the surgical outcome of hemoptysis in patients with various tuberculous pulmonary lesions. A total of 45 cases who underwent surgical procedures for various pulmonary tuberculous lesions with hemoptysis were included in this study. Sixteen patients underwent surgical management within one week of the attack of hemoptysis (group A), the other 29 patients underwent surgery one week after the attack (group B). Hemoptysis was classified into minor, major and massive hemoptysis. Major and massive hemoptysis were the common presentation of group A and tuberculous cavities were the most common lung lesions in both groups (37.7%). Lobectomy was the main surgical procedure performed in both groups (51.1%). Bronchopleural fistula occurred in one case in each group after right pneumonectomy. There was one case (6.2%) of mortality in group A. Tuberculous cavity is the common pulmonary lesion which can result in major and massive hemoptysis, therefore, we recommend early surgical resection of tuberculous cavities to avoid life-threatening hemoptysis. Limited resection should be avoided to prevent recurrence.