Original contribution: sleeve gastrectomy reduces soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in patients with morbid obesity.

BACKGROUND: Early diagnosis of subclinical cardiovascular disease (CVD) in patients with morbid obesity is important. We investigated the effects of sleeve gastrectomy (SG) on serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), oxidized LDL (oxLDL), and other metabolic and inflammatory parameters associated with atherosclerosis in patients with morbid obesity. METHODS: Body mass index (BMI) measurements and assays of metabolic and inflammatory markers were taken in patients in an SG surgery group and a healthy control group and compared at baseline and 12 months after SG. Correlations with changes in these parameters and variations in sLOX-1 were analyzed. RESULTS: Metabolic and inflammatory marker values in the surgery (n = 20) and control (n = 20) groups were significantly different at baseline (p < 0.001). The majority of surgery group biomarker levels significantly decreased with mean BMI loss (- 11.8 ± 9.0, p < 0.001) at 12 months, trending toward control group values. Baseline albumin level as well as percentage reductions in oxLDL and the cholesterol retention fraction (CRF) were found to be significantly correlated with percentage reduction in sLOX-1 at 12 months following SG. CONCLUSION: Metabolic and inflammatory biomarkers elevated at baseline significantly decreased after SG weight loss. Weight loss induced by SG may limit endothelial damage by reducing levels of oxLDL and LOX-1 as assessed by sLOX-1. These findings suggest that sLOX-1 may function as a marker of atherosclerotic disease states in patients with morbid obesity and that metabolic/bariatric surgery can play a meaningful role in CVD prevention.

Association between Bone Mineral Density and Bone Turnover Markers in Breast Cancer Patients and Bone-Only Metastasis.

Background and Objectives: The aim of this study was to determine the influence of bone turnover markers, namely the N-terminal cross-linking telopeptide (NTx) and alpha C-terminal cross-linking telopeptide of type I collagen (α-CTx), in detecting bone metastasis (bone-only) in breast cancer (BC) patients, as well as to determine whether this effect is related to changes in bone mineral density (BMD). Materials and Methods: The participants in this study comprised 30 postmenopausal BC patients with bone metastases (age range: 59.56 ± 9.02), 20 postmenopausal BC patients without bone metastases (age range: 55.30 ± 11.55), and 20 healthy postmenopausal female controls (age range: 55.55 ± 5.85). Bone turnover markers (serum NTx and urine α-CTx) were measured using the ELISA method. A densitometer using dual-energy X-ray absorptiometry (DEXA) was used to analyze the BMD, and tumor markers were measured using the chemiluminescent immunometric assay. Results: The corresponding levels of serum NTx (p = 0.004), parathyroid hormone (PTH) (p = 0.001), and urine α-CTx (p < 0.001) of BC patients were found to be higher than the standard levels. After the BC patients were divided into subgroups on the basis of the presence of metastasis, the urine α-CTx levels (p = 0.001) were seen to be at critically high levels in those patients suffering from BC with metastasis. Though the BMD values in the lumbar spine (p < 0.001) and femoral neck (p = 0.001) were found to be significantly low in BC patients, no statistically substantial difference in the BMD levels of BC patients suffering from metastasis was observed. It was observed that urine α-CTx (specificity: 70%; sensitivity: 85%) values are critical factors that differentiate BC patients with metastasis from BC patients without metastasis. Conclusions: We found that alterations in bone turnover could be detected by using the values of urine α-CTx while differentiating BC patients with metastasis from BC patients without metastasis. Using the biochemical markers of bone turnover and BMD together would be pertinent for determining the level of metastasis present and examining the efficiency of bone density preservation therapy. Ideally, BMD measurement would be evaluated together with biochemical markers.

LOX-1 gene variants and maternal levels of plasma oxidized LDL and malondialdehyde in patients with gestational diabetes mellitus.

PURPOSE: The aim of this study was to investigate the relationships between the maternal levels of oxidized LDL (ox-LDL), lipid peroxidation marker malondialdehyde (MDA) and LOX-1 3'UTR188C/T and K167N single nucleotide polymorphisms in pregnant Turkish women with gestational diabetes mellitus (GDM). METHODS: 116 pregnant women with GDM and 120 healthy pregnant women from the same geographic region were included in the study. Polymerase chain reaction-based restriction analysis was used to identify 3'UTR188C/T and K167N polymorphisms of the LOX-1 gene. Plasma ox-LDL and MDA levels were determined by enzyme-linked immunosorbent assay and spectrophotometric method in all study subjects, respectively. RESULTS: Our results indicated that the distribution of the LOX-1 3'UTR188C/T and K167N genotypes and alleles did not differ significantly among subjects with or without GDM (p > 0.05). TT and NN genotype carriers are associated with some glucose metabolism parameters (p < 0.05). There were no significant differences among plasma ox-LDL and MDA levels with regard to LOX-1 3'UTR188C/T and K167N polymorphisms in GDM group and control subjects (p > 0.05). According to the combined genotype analysis of LOX-1 3'UTR 188 TT and K167N NN polymorphisms, plasma MDA and ox-LDL levels were significantly different between women with GDM and healthy subjects either with or without combined TT/NN genotype carriers (p < 0.001). CONCLUSIONS: According to our results, ox-LDL and MDA levels were increased in GDM pregnant women and healthy pregnant women either with or without combined TT/NN genotype carriers, for our Turkish sample, these genotype carriers appear to be related with increased oxidative stress in patients with GDM.

The association of lectin-like oxidized LDL receptor 1 (LOX-1) K167N and 3'UTR188CT polymorphisms with maternal plasma soluble LOX-1 levels and preeclampsia risk in Turkish population.

PURPOSE: To investigate the main effect of polymorphisms in genes involved in endothelial pathophysiological mechanisms, LOX-1 K167N and 3'UTR188CT single nucleotide polymorphisms (SNPs) in relation to preeclampsia (PE) risk and possible interactions between the gene polymorphisms and plasma oxLDL and soluble LOX-1 (sLOX-1) levels on PE in Turkish population. METHODS: LOX-1 K167N and 3'UTR188CT polymorphisms were studied in 113 pregnant women with preeclampsia and 96 healthy pregnant women by the PCR-RFLP techniques. sLOX-1 and oxLDL levels were determined by enzyme-linked immunosorbent assay (ELISA) in all study subjects. RESULTS: Patients having LOX-1 3'UTR188CT (OR 3.55, 95% CI 1.89-6.67, P = 0.001) or 3'UTR188CC (OR 3.04, 95% CI 1.25-7.38, P = 0.012) genotype had a significantly higher risk of PE than those with 3'UTR188TT genotype. Also, patients having K167N KK (OR 2.73, 95% CI 1.33-5.61, P = 0.005) genotype had a significantly higher risk of PE than those with K167N NN genotype. LOX-1 3'UTR188TT and LOX-1 K167N NN genotype carriers were associated with significantly increased serum sLOX-1 level (P = 0.001). We further investigated the potential combined effect of these polymorphic variants on risk of PE development. According to the combined genotype analysis of LOX-1 3'UTR188TT and K167N NN polymorphisms, sLOX-1 and oxLDL levels also showed significant differences between PE patients and controls with or without combined TT/NN genotype carriers. CONCLUSIONS: Our findings indicate that higher plasma sLOX-1 and oxLDL concentrations, and the LOX-1 3'UTR188C>T and LOX-1 K167N gene polymorphisms were significantly associated with risk of developing preeclampsia. Plasma sLOX-1 may be a potential therapeutic target in the treatment of preeclampsia.

The effects of atorvastatin on oxidative stress in L-NAME-treated rats.

OBJECTIVES: Current evidence suggests that the beneficial vascular effects of statins are not limited to the statins' lipid-lowering properties; these drugs can also improve vascular endothelial cell function. Nω-nitro-l-arginine methyl ester (L-NAME) is a potent synthetic nitric oxide inhibitor, and long-term oral L-NAME treatment is used to induce vascular lesions in experimental animal models. METHODS: We determined the effects of statins on protein carbonyl (PCO), lipid hydroperoxides (LHP), oxidized low-density lipoproteins (ox-LDL) and antioxidants such as paraoxonase 1 (PON1) and total thiols (T-SH) in long-term L-NAME-treated rats. Adult male Wistar rats were divided into three groups, namely, control, L-NAME-treated (1 mg/mL in drinking water for three weeks), and atorvastatin plus L-NAME-treated (4 mg/kg/day atorvastatin for 1 week during the third week of L-NAME treatment) groups. RESULTS: In the L-NAME group, the ox-LDL, LHP and PCO were higher and the PON1 and T-SH were lower than the concentrations observed for the controls. When compared with the L-NAME group, the L-NAME plus atorvastatin group had significantly lower ox-LDL and LHP and higher PON1 activities. Additionally, the elevated total cholesterol (TC) and low-density lipoprotein-C (LDL-C) in the L-NAME group were decreased by atorvastatin administration. TC and LDL-C were positively correlated with ox-LDL and LHP and negatively correlated with PON1 in all groups. High-density lipoprotein-C (HDL-C) was negatively correlated with ox-LDL. CONCLUSION: PON1 prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids; its activity showed a pronounced decrease in the L-NAME treatment group and was increased in the atorvastatin group. Based on our findings, we concluded that the atorvastatin had HDL-related antioxidant activity as well as lipid-lowering properties.

Circulating nuclear factor-kappa B mediates cancer-associated inflammation in human breast and colon cancer.

BACKGROUND: Inflammation is recognized as a hallmark feature of cancer development and progression. The aim of our study was to investigate the significance of serum nuclear factor kappa-B (NF-κB) levels as a circulating marker in the monitoring of inflammation in breast and colon cancer; to show the relationship between NF-κB with inflammatory parameters as tumour necrosis factor-α (TNF-α), soluble TNF-related apoptosis-inducing ligand (sTRAIL), interleukin-6 (IL-6), pentraxin-3 (PTX-3), procalcitonin (PCT), and C-reactive protein (CRP) levels. METHODS: Serum NF-κB, TNF-α, sTRAIL, IL-6, PTX-3, PCT, and serum CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) in 40 patients with breast cancer, 40 patients with colon cancer and 30 healthy controls. RESULTS: The serum NF-κB, TNF-α, IL-6, PTX-3, PCT, and serum CRP concentration was significantly higher, and the serum sTRAIL concentration was significantly lower in the patients with breast and colon cancer than in healthy controls. NF-κB was positively correlated with CRP and negatively correlated with sTRAIL. CONCLUSIONS: These results suggest that increased NF-κB may decrease the clinical efficacy of sTRAIL in solid tumour cells. There is a relationship between inflammation and carcinogenesis so that the development of cancer occurs with chronic inflammation in breast and colon. The study results have shown that colon and breast cancer patients have increased systemic inflammation, as measured by increased circulating cytokines, and acute-phase proteins, or by abnormalities in circulating cells. NF-κB may combine with other markers of the systemic inflammatory response in prognostic scores in cancer. In addition to surgical resection of the tumour, and conventional radio and chemotherapy for cancer treatment, the use of sTRAIL or other agonists for cancer therapy appeared a new potential therapy.

The evaluation of oxidative stress parameters in breast and colon cancer.

ABSTRACT: Our aim in this study was to investigate the relationship between serum ischemia modified albumin (IMA) levels with oxidative stress parameters [protein carbonyl (PCO), advanced protein oxidation products (AOPPs), malondialdehyde (MDA), total nitric oxide (NOx), prooxidant-antioxidant balance (PAB), and ferric reducing of antioxidant power (FRAP)] in breast cancer (BC) and colon cancer (CC).In total, 90 patients undergoing surgical treatment for BC (n = 45) or CC (n = 45) and 35 healthy controls were included in this cross-sectional study.The serum PCO, AOPPs, MDA, NOx, PAB, and IMA levels were all statistically significantly higher in the cancer patients than in the control group. MDA, NOx, and PAB levels were significantly lower in the BC group than in the CC group. FRAP values were statistically significantly lower in both the CC group and the BC group compared to the control. IMA showed a weak positive correlation with CA-19.9 (r = 0.423 P = .007) but a moderate positive correlation with tumor size in the CC group. IMA showed a positive correlation with metastasis, grade, and HER2 and a negative correlation with ER and PR in the BC group.Oxidative stress is a key player in the development of solid malignancies. Cancer development is a multistage process, and oxidative stress caused by the production of ROS/RNS in the breast and colon may predispose individuals to BC and CC. Patients with BC and CC had an impaired oxidative/antioxidant condition that favored oxidative stress. The ROC analysis indicated that IMA sensitivity above 80% could be used as a secondary biomarker in diagnosis.

Systemic Amelioration via Curcumin in Rats following Splenectomy: Lipid Profile, Endothelial and Oxidative Damage.

BACKGROUND: We investigated the postsurgical effects of splenectomy with additional curcumin therapy, as an antioxidant, anti-inflammatory substance among the lipid profile and histopathological changes. MATERIALS AND METHODS: 32 rats were randomly divided into four groups: control group (L): laparotomy, sham group: splenectomy (S), splenectomy group treated with curcumin (SC) and splenectomy group treated with corn oil (SCO) for 28 days. The primary outcomes; total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), oxidized LDL (ox-LDL) very-low-density lipoprotein (VLDL) and lectin-type oxidized LDL receptor 1 (LOX-1), secondary outcomes: nuclear factor kappa B (NF-кB), malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) were measured. Histopathological changes were examined in vascular, intestinal and lung tissues. The analysis was performed by ANOVA. RESULTS: TG, LDL, ox-LDL, and LOX-1 elevated in S group while reduced by curcumin compared with L group (p < 0.05). Serum and tissue levels of NF-кB and MDA were higher in S group and lower in SC group than L group (p < 0.05). Serum and intestinal levels of SOD and GPx increased in L group while reduced by curcumin (p < 0.05). Total histopathological scores of intestinal tissues were higher in S and SCO groups compared to L and SC groups (p < 0.05). No major changes in vascular and lung tissues were observed except the lymphoid follicles which was higher in S and SCO groups compared to L and SC groups (p < 0.05). CONCLUSIONS: Curcumin partially improved the lipid profile dysfunction by modulating NF-кB, MDA, SOD, and GPx in splenectomized rats while less likely improving any vascular and alveolar regeneration.

Evaluation of the relationship between serum ghrelin levels and cancer cachexia in patients with locally advanced nonsmall-cell lung cancer treated with chemoradiotherapy.

BACKGROUND: Ghrelin plays a role in mechanisms related to cancer progression - including cell proliferation, invasion and migration, and resistance to apoptosis in the cell lines from several cancers. We investigated the role of ghrelin levels in cancer cachexia-anorexia in patients with locally advanced nonsmall-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). MATERIALS AND METHODS: This study involved 84 NSCLC patients who had received concomitant CRT. Blood ghrelin levels were compared before and 3 months after CRT. Meanwhile, changes in body weight of the patients were also investigated with changes in ghrelin levels before and after CRT. RESULTS: Ghrelin levels were significantly decreased in line with changes in patients' weights in patients receiving CRT (P < 0.001). Serum albumin levels and inflammatory-nutritional index were significantly decreased after radiotherapy (RT) (3.01 ± 0.40 g/dL, 0.38 ± 0.20) when compared with its baseline levels (3.40 ± 0.55 g/dL,P < 0.001; 0.86 ± 0.71,P < 0.001, respectively). Serum C-reactive protein levels were significantly increased after CRT (7.49 ± 6.53 mg/L) when compared with its baseline levels (9.54 ± 3.80 mg/L,P = 0.038). After RT, ghrelin levels in patients were positively correlated with body mass index (r = 0.830,P < 0.001) and albumin (r = 0.758,P < 0.001). CONCLUSION: Ghrelin may play a role in the pathogenesis of weight loss in NSCLC patients. Ghrelin seems to be implicated in cancer-related weight loss. Ghrelin, cancer, and RT all together have a role in tumor-related anorexia-cachexia in patients with NSCLC. Results of this study need further evaluation as regards to its potential role as an adjuvant diagnostic or prognostic marker.

Polycystic ovary syndrome and endothelial dysfunction: A potential role for soluble lectin-like oxidized low density lipoprotein receptor-1.

The aims of this study were to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), oxidized LDL (oxLDL), paraoxonase-1(PON-1) and hydroperoxide (LOOH) levels are altered in women with polycystic ovary syndrome (PCOS) and also to determine if hyperandrogenism, insulin resistance (IR) and Anti-Müllerian Hormone (AMH) are associated with endothelial dysfunction in PCOS. A total of 46 women with PCOS and 46 non-PCOS healthy controls were recruited. Women with PCOS had significantly higher sLOX-1, oxLDL and LOOH concentrations than non-PCOS women [6.16 (3.92-13.95) vs 1.37 (0.63-4.43) ng/mL, p < 0.001; 6.48 ± 1.03 vs 3.16 ± 1.02 µU/L, p < 0.001; 2.45 (1.45-3.45) vs 1.06 (0.64-1.56) µmol/L, p < 0.001]. The mean PON-1 level of PCOS group was lower than non-PCOS group (69.47 ± 10.75 vs 104.08 ± 21.43 U/mL, p < 0.001). There was no significant difference in terms of the sLOX-1, oxLDL, LOOH and PON-1 levels between normal weight and overweight PCOS women. On univariate logistic regression analysis, Ferriman-Gallwey scale (FGS), HOMA-IR and AMH were an independent predictors of high risk group of endothelial dysfunction markers (HR-EDm). Age and BMI were not associated with HR-EDm. When incorporated into the multivariate model, endotelial dysfunction markers independently correlated with clinical hyperandrogenism (FGS) but not with AMH. In conclusion, our results indicated that an increased concentration of sLOX-1 might be an early predictor of endothelial damage in patients with PCOS. Women with PCOS have elevated sLOX-1, oxLDL, LOOH and decreased PON-1 levels, independent of BMI. Endothelial dysfunction in women with PCOS is associated with hyperandrogenism. Further studies are required to confirm our findings.

Relationships between visceral/subcutaneous adipose tissue FABP4 expression and coronary atherosclerosis in patients with metabolic syndrome.

BACKGROUND: Cytoplasmic fatty acid-binding proteins facilitate the transport of lipids to specific compartments in cells. Fatty acid-binding protein 4 (FABP4), also known as aP2 or A-FABP, plays a key role in the development of atherosclerosis, insulin resistance, obesity, and metabolic syndrome (MS). The FABP4 polymorphisms are associated with protein expression changes in vitro and metabolic and vascular alterations in vivo. The aim of this study was to investigate the association between FABP4 messenger ribonucleic acid (mRNA) expression levels in epicardial (EAT), pericardial (PAT), and subcutaneous adipose tissues (SAT), and the extent of coronary atherosclerosis in coronary artery disease (CAD) patients with MS. Furthermore, the relationship between the extent of coronary atherosclerosis and epicardial adipose tissue volume (EATV) and FABP4 gene variations was evaluated. PATIENTS AND METHODS: A total of 37 patients undergoing coronary artery bypass grafting because of CAD (MS CAD group) and 23 non-MS patients undergoing heart valve surgery (control group) were included. Coronary angiography was performed for all patients and the extent of coronary atherosclerosis was assessed using the Sullivan's scoring system. The mRNA expression levels of FABP4 gene in EAT, PAT, and SAT, and FABP4 polymorphisms were analyzed using the quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: An increased FABP4 expression was observed in EAT and PAT of MS CAD group compared to controls. In the MS CAD group, FABP4 mRNA expression levels in EAT was 2.8-fold higher compared to PAT. The expression of FABP4 in EAT was positively correlated with the extent of atherosclerosis and EATV in MS CAD group (r = 0.588, P= 0.001, r = 0.174, P = 0.001, respectively). There were no correlations between PAT and SAT versus the extent of atherosclerosis and EATV. The FABP4 EAT mRNA expression levels were found to significantly increase in mutant allele carriers of rs1054135, whereas they significantly decreased in mutant allele carriers of rs77878271 (T-87C) in MS CAD group (P < 0.05). The extent of atherosclerosis was also found to be significantly associated with rs1054135 (P < 0.05). A cut-off point of 57.5 cm3 EATV was used indicating the presence of CAD with a significant area under the curve of 0.783%, 98% sensitivity, and 100% specificity (95% CI 0.620-0.880; P < 0.05). CONCLUSIONS: Our study results suggest that FABP4 expression in EAT is strongly associated with the extent of atherosclerosis and EATV in MS CAD patients.

Associations Between miRNAs and Two Different Cancers: Breast and Colon.

OBJECTIVE: Screening approaches using microRNAs (miRNAs) have been gaining increased attention owing to their potential applications in the diagnosis, prognosis, and monitoring of cancer, because aberrant miRNA expression plays a role in the development and advancement of malignancies. The objectives of this study were to characterize mir21, miR31, mir143, mir145, and control RNU43, which are differentially expressed in peripheral blood mononuclear cells (PBMCs) of breast and colorectal cancer patients, compared to that in controls and to establish whether this is specific to breast and colon cancer for use as tumor markers. METHODS: Thirty newly diagnosed patients with breast cancer and 30 patients with colorectal cancer were enrolled together with 30 healthy controls. PBMCs were isolated from venous blood samples of individuals. Next, miRNA expression analysis was performed by a two-step method of reverse transcription and qPCR. RESULTS: The expression levels of miR-143 and miR-31 were significantly decreased, whereas the expression levels of miR-145 and miR-21 were significantly increased in breast cancer patients compared to those in healthy subjects. Moreover, the expression levels of miR-143, miR-145, and miR-21 were significantly increased and, in contrast, the changes in the expression levels of miR-31 were not statistically significant in colon cancer compared to those in healthy subjects. miR-21 exhibited the highest increase in both breast and colon cancers. There was a weak positive correlation between miR-145 and CA-15.3 in patients with breast cancer (r = 0.451; p = 0.012). miR-143 was positively correlated with the TNM stage in colon cancer patients (r = 0.568; p = 0.001). CONCLUSION: A biomarker panel composed of miR-21, miR-31, miR-143, and miR-145 in PBMC may provide a new diagnostic approach for the early detection of breast and colon cancer. As miR-21 expression was found to be the highest among all the miRNAs evaluated, it may represent a new tumor biomarker and a candidate therapeutic drug or gene target in colon and breast cancer.

The Relationship between Plasma Taurine Levels and Diabetic Complications in Patients with Type 2 Diabetes Mellitus.

Background: Taurine has an active role in providing glucose homeostasis and diabetes causes a decline in taurine levels. This paper investigates the relationship between taurine and diabetic complications, patients' demographic features, and biochemical parameters. Methods: Fifty-nine patients with type 2 diabetes mellitus (T2DM), and 28 healthy control subjects between the ages of 32 and 82 were included in the study. The mean age of subjects was 55.6 ± 10.3 and mean diabetes duration was 10.2 ± 6.0 years. The most commonly accompanying comorbidity was hypertension (HT) (64.5%, n = 38), and the most frequent diabetic complication was neuropathy (50.8%, n = 30). Plasma taurine concentrations were measured by an enzyme-linked immunoassay (ELISA) kit. Results: Plasma taurine concentrations were significantly lower in diabetic patients (0.6 ± 0.1 mmol/L) than controls (0.8 ± 0.2 mmol/L) and in hypertensive (0. 6 ± 0.1 mmol/L) patients (p = 0.000, p = 0.027 respectively). Conclusion: Plasma taurine levels were decreased in patients with T2DM and this was not related to FBG, HbA1c, and microalbuminuria. With regard to complications, we only found a correlation with neuropathy. We suggest that taurine levels may be more important in the development of diabetes; however, it may also have importance for the progression of the disease and the subsequent complications. We further assert that taurine measurement at different times may highlight whether there is a causal relationship in the development of complications.

Evaluation of plasma antimicrobial peptide LL-37 and nuclear factor-kappaB levels in stable chronic obstructive pulmonary disease.

BACKGROUND: Antimicrobial peptides are effectors of host defence against infection and inflammation and can encourage wound repair. OBJECTIVES: The objectives of this study were to investigate the plasma antimicrobial peptide LL-37 and nuclear factor-kappaB (NF-κB) levels in patients with stable COPD compared with a control group and to highlight their importance in immune inflammation. METHODS: One hundred and thirty-eight stable COPD patients and 33 control subjects were enrolled in the study. The COPD patients were classified into four groups based on FEV1 (groups I-IV) and also divided into "low-risk and high-risk" groups (groups A-B [low risk], C-D [high risk]). RESULTS: Plasma LL-37 levels were significantly lower while plasma NF-κB levels of the COPD patients were significantly higher than those of the control subjects (P<0.001, both). LL-37 levels were significantly lower in group IV than in groups I, II, and III (P<0.01, all). NF-κB levels were significantly higher in groups III and IV than in groups I and II (P<0.05, both). There was a positive correlation between FEV1 and FEV1/FVC in all COPD patients (r=0.742, P<0.001) and in group D (r=0.741, P<0.001). Furthermore, there was an inverse correlation between LL-37 and NF-κB in both the groups C (r=-0.566, P<0.001) and D (r=-0.694, P<0.001) and group C+D combined (r=-0.593, P<0.001). Furthermore, in group C, LL-37 and FEV1 were positively correlated (r=0.633, P<0.001). CONCLUSION: Our study indicated that plasma LL-37 and NF-κB may play an important role in chronic immune inflammation. Decreased LL-37 levels may be particularly high risk for patients in stage IV disease. The role of LL-37 as a target for treatment of the immune system and COPD must be widely evaluated.

Clinical Value of Circulating Microribonucleic Acids miR-1 and miR-21 in Evaluating the Diagnosis of Acute Heart Failure in Asymptomatic Type 2 Diabetic Patients.

To investigate whether the circulating miR-1 (microRNA-1) and miR-21 expression might be used in the diagnosis of heart failure (HF) and silent coronary artery disease (SCAD) in asymptomatic type 2 diabetes mellitus (T2DM) patients and to explore the relationship of these miRs with N-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3. One hundred thirty-five consecutive patients with T2DM and 45 matched control subjects were enrolled in the study. This study consisted of the following four groups: control group (mean age: 60.23 ± 6.27 years, female/male (F/M): 23/22); diabetic group (DM) (mean age: 61.50 ± 5.08, F/M: 23/22); DM + SCAD group (mean age: 61.61 ± 6.02, F/M: 20/25); and DM + acute HF group (mean age: 62.07 ± 5.26 years, F/M: 20/25). miR-1 was downregulated in the DM, CAD + DM and HF + DM groups by 0.54, 0.54, and 0.12 fold as compared with controls, respectively. The miR-1 levels were significantly lower in HF + DM than DM with 0.22 fold changes (p < 0.001); and in patients with CAD + DM group with 0.22 fold changes (p < 0.001). Similarly, miR-21 was overexpressed in patients with DM, CAD + DM, and HF + DM with 1.30, 1.79 and 2.21 fold changes as compared with controls, respectively. An interesting finding is that the miR-21 expression was significantly higher in the HF + DM group as compared with the CAD + DM group; miR-1 was negatively correlated with NT-proBNP (r = -0.891, p < 0.001) and galectin-3 (r = -0.886, p < 0.001) in the HF + DM group; and miR-21 showed a strongly positive correlation with (r = 0.734, p < 0.001) and galectin-3 (r = 0.764. p < 0.001) in the HF + DM group. These results suggest that the circulating decreased miR-1 and increased miR-21 expression are associated with NT-proBNP and galectin-3 levels in acute HF + DM. Especially the miR-21 expression might be useful in predicting the onset of acute HF in asymptomatic T2DM patients. The miR-21 expression is more valuable than the miR-1 expression in predicting cardiovascular events of acute HF and the combined analysis of miR-21 expression, galectin-3, and NT-proBNP can increase the predictive value of miR-21 expression.

Changes in inflammatory mediators as a result of intermittent hypoxia in obstructive sleep apnea syndrome.

BACKGROUND: Inflammation plays an important role in obstructive sleep apnea syndrome (OSAS). The objective of this study was to investigate the relationship of serum C-reactive protein (CRP), pentraxin-3 (PTX-3), procalcitonin (ProCT), interleukin-33 (IL-33) and its soluble receptor ST2 (sST2) with the syndrome severity and to show theirs importance as biomarkers. METHODS: This study comprises a total of 84 identical (sex and age wise) cases. Full-night polysomnography was performed in each patient. OSAS diagnosis and severity index being based on the widely used criterion known as Apnea Hypopnea Index(AHI). Subgroups were as follows: 24(AHI < 5) controls, 28 mild-moderate OSAS(AHI 5-30) and 32 severe OSAS(AHI > 30). RESULTS: PTX-3, IL-33 and sST2 receptors were significantly higher in OSAS groups than the control group (P < .001). However, both CRP and ProCT levels were similar in all subjects. There was a positive correlation between PTX-3 and BMI (r = 0.446; P < .01), ODI (r = 0.555; P < .01), IL-33 (r = 0.348; P = .001) and sST2 (r = 326; P = .002), while there was a negative correlation with minimum SaO2 (r = -0.672; P < .01) in patient group. PTX-3 as a predictor of OSAS showed highest specificity (%91.7) and sensitivity (%91.7) (P < .001). CONCLUSIONS: PTX-3 can be a new indicator reflecting the inflammatory state in patients with OSAS. Since patients with OSAS could have more hypoxic state during sleep, we found higher PTX-3 level in those patients and a negative correlation between PTX-3 and minimum SaO2 , which could explain that PTX-3 levels can increase with the severity of disease. Our results suggest that PTX-3 as an inflammatory biomarker may play a crucial role as an indicator of syndrome severity in OSAS.

YKL-40, Soluble IL-2 Receptor, Angiotensin Converting Enzyme and C-Reactive Protein: Comparison of Markers of Sarcoidosis Activity.

The aims of this study were to describe the clinical, radiological and immunological features of a population of sarcoidosis patients and to analyse chitinase-3-like protein 1 (YKL-40), soluble interleukin-2 receptor (sIL-2R), neopterin concentrations and adenosine deaminase (ADA) activity in serum of these patients in order to understand their potential as disease markers. Fifty-nine patients affected by chronic sarcoidosis, in active (20 patients) and inactive (39 patients) phase according to the clinical, radiological and laboratory criteria were studied. Serum YKL-40, sIL-2R, high-sensitive C-reactive protein (hs-CRP), neopterin levels and ADA activities were evaluated and compared with those of 25 healthy controls. Individuals with chronic sarcoidosis were significantly higher serum YKL-40, sIL-2R, neopterin, hs-CRP concentrations, angiotensin converting enzyme (ACE) and ADA activity than those of control subjects. Sarcoidosis patients in the active phase of the disease were significantly higher YKL-40, sIL-2R, hs-CRP levels and ACE activity than those in the inactive phase, while ADA activities and neopterin levels did not display any significant difference between the active and inactive disease groups. In comparison to the other parameters, as panel measurement of the serum YKL-40, sIL-2R, ACE and hs-CRP indicate a greater discrimination between active and inactive disease. The results indicate that serum YKL-40, sIL-2R, ACE and hs-CRP concentrations may be useful marker for monitoring sarcoidosis disease activity.

The Relationship Between Lipid Peroxidation and LDL Desialylation in Experimental Atherosclerosis.

ABSTRACT High serum total cholesterol concentration has been strongly connected with atherosclerosis in numerous studies. Being the main carrier of cholesterol in blood, low-density lipoprotein (LDL) is also the principal lipoprotein causing atherosclerosis. Sialic acids are a family of amino sugars that are commonly found as terminal oligosaccharide residues on glycoproteins and are sialylated on their apolipoprotein and glycolipid constituents. In several studies, it was demonstrated that LDL has a 2.5- to 5-fold lower content of sialic acid in patients with coronary artery disease compared with healthy subjects. The role of oxidatively modified LDL in the pathogenesis has been well documented. These studies have focused on modifications in the lipid and protein parts of LDL. But recently, desialylated LDL and its relation with the oxidation mechanisms have received attention in the pathogenesis of atherosclerosis and coronary artery disease (CAD). From these points, we have performed atheroma plaques in an experimental atherosclerosis model with rabbits and examined the LDL and plasma sialic acid and thiobarbituric acid reactive substance (TBARS) levels in the same model. We also have determined serum sialidase enzyme activities relevant with these parameters. LDL sialic acid levels were significantly decreased in the progression of the atherosclerosis (by the 30th, 60th, and 90th days). LDL and plasma TBARS levels and plasma sialidase enzyme activities were significantly elevated by the same time periods. In conclusion, serum sialidase enzyme may play an important role in the desialylation mechanism, and reactive oxygen substance (ROS) may affect this reaction.

The relationship between circulating irisin, retinol binding protein-4, adiponectin and inflammatory mediators in patients with metabolic syndrome.

OBJECTIVE: We wanted to investigate whether there is a relationship between circulating irisin, retinol binding protein-4 (RBP-4), adiponectin and proinflammatory mediators implicated in the development of insulin resistance (IR) in metabolic syndrome (MetS). SUBJECTS AND METHODS: In 180 individuals, including controls and patients with MetS, we measured fasting plasma insulin, high sensitivity C-reactive protein (hsCRP), pentraxin-3 (PTX-3), interleukin-33 (IL-33), irisin, RBP-4, and adiponectin using ELISA kits. RESULTS: While fasting plasma hsCRP, PTX-3, IL-33, irisin, RBP-4 concentrations were higher, adiponectin levels were lower in patients with MetS than in controls. A correlation analysis revealed that plasma irisin levels were positively associated with MetS components such as waist circumference and waist-hip ratio, low density lipoprotein (LDL) and markers of systemic inflammation such as PTX-3, hsCRP, uric acid, and RBP-4. Adiponectin levels were negatively associated with waist circumference, waist-hip ratio, PTX-3 and LDL. CONCLUSIONS: Although the precise mechanisms are still unclear, irisin, RBP-4, adiponectin and PTX-3 are hallmarks of the MetS, which is related to low-grade inflammation. It is conceivable that irisin and adiponectin might contribute to the development of MetS and may also represent novel MetS components. Future clinical studies are needed to confirm and extend these data.

Bone metabolism in ovariectomized rats with induced hyperthyroidism: the effect of estrogen replacement.

We aimed to investigate whether or not the estrogen is playing any role in the effect of thyroid hormones on bone metabolism. The rats were divided into five groups. In the first group L-thyroxine-induced hyperthyroid rats were ovariectomized (OVX) while the OVX rats were administered L-thyroxine in the second group. 17beta-Estradiol (E2) was replaced in OVX rats in Group III. L-thyroxine and E2 were simultaneously administered to OVX rats in Group IV. The fifth group received sham operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)alpha, calcium (Ca), phosphorous (P), parathyroid [corrected] hormone (PTH), alkaline phosphatase (t-ALP), bone-specific alkaline phosphatase (b-ALP) and E2. The levels of cytokines, t-ALP and b-ALP increased but PTH decreased, while there was no change in Ca and P levels in L-thyroxine-administrated rats. However, the levels of cytokines, Ca, P, PTH, t-ALP and b-ALP did not change in L-thyroxine-administered OVX rats. In OVX rats, the cytokines, t-ALP and b-ALP increased while Ca, P remained the same, but PTH decreased. L-thyroxine administration to OVX rats did not change the cytokines, Ca, P, PTH, t-ALP and b-ALP levels. The replacement of E2 in OVX rats decreased the cytokines, t-ALP and b-ALP values, increased PTH levels while there was no change in Ca and P. L-thyroxine and E2 administration to OVX rats increased the cytokines, t-ALP and b-ALP levels and decreased PTH, but Ca and P remained the same. In sham-operated rats, there was no change in all parameters compared to initial values. This study suggests that estrogen may play a role in the effects of thyroid hormones on bone metabolism.