Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study.

PURPOSE: This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). METHODS: Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. RESULTS: Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. CONCLUSIONS: TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results.

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.

The Effect of Menstrual Cycle Phase on the Prognostic Factors in Patients with Premenopausal Breast Tumors.

Background: Estrogen receptor and progesterone receptor positivity and c-erbB2 gene expression levels are important in determining breast cancer development and aggression. Although the importance of hormonal factors in tumor cell proliferation, migration and differentiation is increasing, it needs more evidence. The effect of BC surgery timing during the menstrual cycle on prognosis remains controversial. In order to clarify this hypothesis, we aimed to determine the importance of adjusting the timing of surgery according to the menstrual cycle by examining the relationship between estrogen receptor, progesterone receptor, c-erbB2 gene and the menstrual cycle phase in patients with premenopausal breast cancer. Method: Our study was designed retrospectively. 50 patients with premenopausal breast cancer who were operated were included in the study. Results: Our results showed that the patients in the luteal phase had higher ER positivity, PR positivity and c-erbB2 negativity, and the number of metastatic axillary lymph nodes was lower than the patients in follicular phase. Conclusions: BC surgery during the luteal phase in pre-menopausal women is associated with a better clinical outcome. Although larger-scale studies are needed, our results suggest that better results can be achieved by performing surgery in luteal phase in BC patients during premenopausal period.

Remote myocardial injury: the protective role of fluoxetine.

Aortic cross-clamping-induced ischemia-reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.

The effects on oxidative DNA damage of laparoscopic gastric band applications in morbidly obese patients.

BACKGROUND: Obesity may induce oxidative stress, causing oxidative damage of DNA. We examined associations between decreasing serum and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and weight loss in morbidly obese patients before and 6 months after laparoscopic adjustable gastric banding (LAGB). METHODS: We compared patients who had surgery for morbid obesity with healthy, nonobese controls. Urine and fasting blood samples were collected once from the controls and from the morbidly obese patients before and 6 months after the LAGB. The serum and urinary 8-OHdG levels were evaluated in these groups using an enzyme-linked immunosorbent assay kit. RESULTS: We included 20 patients who had surgery for morbid obesity (8 men, 12 women, mean body mass index [BMI] 46.82 ± 4.47) and 20 healthy, nonobese people (10 men, 10 women, mean BMI 22.52 ± 2.08) in our study. There was no significant difference in serum 8-OHdG levels between the groups, whereas urinary 8- OHdG levels were significantly higher in morbidly obese patients than in controls. Weight, BMI and serum and urinary 8-OHdG levels were significantly decreased in morbidly obese patients 6 months after LAGB. CONCLUSION: The LAGB provides efficient weight loss in patients with morbid obesity. The systemic oxidative DNA damage was increased by the morbid obesity, but this increase was not related to weight gain, and it was more evident in serum than urine samples. After LAGB for morbid obesity, the oxidative DNA damage declined both in serum and urine.

CONTEXTE: L'obésité peut provoquer stress oxydatif qui endommage l'ADN. Nous avons analysé les liens entre une baisse des taux de 8-OHdG (8-hydroxy-2'-désoxyguanosine) sériques et urinaires et la perte de poids chez des patients atteints d'obésité morbide avant, puis 6 mois après la pose d'un anneau gastrique ajustable par laparoscopie (AGAL). MÉTHODES: Nous avons comparé des patients qui ont subi cette chirurgie pour un problème d'obésité morbide à des témoins non obèses en bonne santé. Nous avons prélevé des échantillons d'urine et de sang à jeun chez les témoins 1 fois et chez les patients atteints d'obésité morbide, avant, puis 6 mois après l'intervention pour AGAL. Les taux de 8-OHdG sériques et urinaires ont été mesurés dans les 2 groupes à l'aide d'une trousse de test ELISA (enzyme-linked immunosorbent assay). RÉSULTATS: Notre étude a inclus 20 patients soumis à la chirurgie pour obésité morbide (8 hommes, 12 femmes; indice de masse corporelle [IMC] moyen 46,82 ± 4,47) et 20 témoins non obèses en bonne santé (10 hommes, 10 femmes; IMC moyen 22,52 ± 2,08). Nous n'avons noté aucune différence significative des taux de 8-OHdG sériques entre les 2 groupes, mais les taux de 8-OHdG urinaires étaient significativement plus élevés chez les patients souffrant d'obésité morbide que chez les témoins. Le poids, l'IMC et les taux de 8-OHdG sériques et urinaires avaient significativement diminué chez les patients atteints d'obésité morbide 6 mois après l'intervention pour AGAL. CONCLUSION: L'AGAL est une technique efficace de perte de poids chez les patients souffrant d'obésité morbide. L'atteinte oxydative systémique de l'ADN était exacerbée par l'obésité morbide, mais cette hausse n'était pas reliée au gain pondéral, et elle était plus évidente dans les échantillons sériques que dans les échantillons urinaires. Après la pose d'un AGAL pour obésité morbide, l'atteinte oxydative de l'ADN a diminué dans le sérum et dans l'urine.

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.

Can circulating oxidative stress-related biomarkers be used as an early prognostic marker for COVID-19?

Background: Oxidative stress plays an important role in the pathogenesis of many diseases. This study aimed to investigate the relationship between nuclear factor kappa B (NF-κB) and oxidative stress and the severity of the disease in new COVID-19 patients, and, to compare the levels of NF-κB, oxidized LDL (oxLDL), and lectin-like oxidized-LDL receptor-1 (LOX-1) with oxygen saturation, which is an indicator of the severity parameters of the disease in COVID-19 patients. Methods: In this prospective study, 100 COVID-19 patients and 100 healthy subjects were selected. Results: LOX-1, NF-κB, and oxLDL were found to be higher in COVID-19 patients compared to the healthy subjects (p < 0.001 for all). According to the results of correlation analysis, it was found that there was no significant relationship between oxygen saturation and LOX-1, NF-κB and oxLDL parameters. There was significant relationship between oxLDL with LOX-1 and NF-κB in patients with COVID-19 disease. ROC analysis results of the highest discrimination power were oxLDL (AUC: 0.955, CI: 0.904-1.000; sensitivity: 77%, and specificity: 100%, for cutoff: 127.944 ng/l) indicating COVID-19. Conclusion: Oxidative stress plays an essential role in COVID-19. NF-κB, oxLDL, and LOX-1 seem to represent good markers in COVID-19. Our study also showed that oxLDL has the highest power in distinguishing patients with COVID-19 from the healthy subjects.

Significance of Plasma Irisin, Adiponectin, and Retinol Binding Protein-4 Levels as Biomarkers for Obstructive Sleep Apnea Syndrome Severity.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder that is caused by the reduction or cessation of airflow in the upper airway. Irisin, retinol-binding protein-4 (RBP-4), and adiponectin are the three significant factors in the metabolic process of the human body. The objective of this study was to investigate whether plasma irisin, RBP-4, and adiponectin levels are associated with the severity of OSAS. METHODS: According to inclusion and exclusion criteria, 125 patients with OSAS and 46 healthy, gender-matched controls were included in this study. The patients were classified according to the apnea hypopnea index (AHI) as 14 mild cases (5 < AHI < 15), 23 moderate OSAS cases (15 < AHI < 30), and 88 severe OSAS cases (AHI > 30). The plasma irisin, RBP-4, and adiponectin levels were measured and compared between groups. RESULTS: RBP-4 levels were higher in severe OSAS compared to other groups, and irisin levels were significantly lower in severe OSAS compared to other groups. There was a negative correlation between irisin and RBP-4 (r = -0.421; p < 0.001), and irisin and AHI (r = -0.834; p < 0.001), and a positive correlation between irisin and adiponectin (r = 0.240; p = 0.002). There was a negative correlation between RBP-4 and adiponectin (r = -0.507; p < 0.001) and a positive correlation between RBP-4 and AHI (r = 0.473; p < 0.001). As a predictor of OSAS, adiponectin showed the highest specificity (84.8%) and RBP-4 the highest sensitivity (92.0%). CONCLUSION: Circulating adiponectin, irisin, and RBP-4 may be new biomarkers in OSAS patients in addition to risk factors such as diabetes, obesity, and hypertension. When polysomnography is not available, these parameters and clinical data can be used to diagnose the disease. As a result, patients with an AHI score greater than thirty should be closely monitored for metabolic abnormalities.

Maternal serum preptin levels in the pathogenesis and diagnosis of Gestational diabetes mellitus.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy that increases both maternal and fetal mortality and morbidity. It was investigated whether there is a change in circulating levels of preptin, a new peptide secreted from pancreatic beta cells, due to GDM in pregnant women. The relationship between serum preptin levels with insulin and other metabolic parameters was also evaluated in these subjects. Methods: Eighty-five patients diagnosed as GDM and 89 healthy pregnant women with 75 mg oral glucose tolerance test (OGTT) was assessed in terms of serum preptin levels. Results: The serum preptin levels of the GDM group were significantly higher than those of the control group (p=0.001; p < 0.01). For the cutoff value of preptin measurement of 335.3 ng/L, the sensitivity was 97.65%, specificity was 87.64%, positive predictive value was 88.3% and negative predictive value was 97.5%. The risk of developing the disease is 294.273 times higher in patients with preptin level of 335.3 and above. Conclusions: We think that the reason for the increase in serum preptin levels in GDM is probably the response to glucose. The current results indicate that preptin plays an important role in elucidating the pathology of GDM. In addition, the search for a practical marker for the diagnosis of GDM suggests that the measurement of preptin level is promising.

Prediction of Preterm Delivery Using Serum Ischemia Modified Albumin, Biglycan, and Decorin Levels in Women with Threatened Preterm Labor.

OBJECTIVE: The serum ischemia modified albumin (IMA), biglycan, and decorin levels of pregnant women who were hospitalized for threatened preterm labor were measured. METHODS: Fifty-one consecutive pregnant women with a single pregnancy between the 24th and 36th weeks with a diagnosis of threatened preterm labor were included in the present prospective cohort study. RESULTS: As a result of multivariate logistic regression analysis for predicting preterm delivery within 24 hours, 48 hours, 7 days, 14 days, ≤ 35 gestational weeks, and ≤ 37 gestational weeks after admission, area under the curve (AUC) (95% confidence interval [CI[) values were 0.95 (0.89-1.00), 0.93 (0.86-0.99), 0.91 (0.83-0.98), 0.92 (0.85-0.99), 0.82 (0.69-0.96), and 0.89 (0.80-0.98), respectively. In the present study, IMA and biglycan levels were found to be higher and decorin levels lower in women admitted to the hospital with threatened preterm labor and who gave preterm birth within 48 hours compared with those who gave birth after 48 hours. CONCLUSION: In pregnant women admitted to the hospital with threatened preterm labor, the prediction preterm delivery of the combined model created by adding IMA, decorin, and biglycan in addition to the TVS CL measurement was higher than the TVS CL measurement alone. CLINICAL TRIAL REGISTRATION: The present trial was registered at ClinicalTrials.gov, number NCT04451928.

OBJETIVO: Medir os níveis séricos de albumina modificada por isquemia (IMA), biglicano e decorina de gestantes hospitalizadas por ameaça de parto prematuro. MéTODOS: Cinquenta e uma mulheres grávidas consecutivas com uma única gravidez entre a 24ª e a 36ª semanas com diagnóstico de ameaça de trabalho de parto prematuro foram incluídas no presente estudo de corte prospectivo. RESULTADOS: Como resultado da análise de regressão logística multivariada para prever parto prematuro dentro de 24 horas, 48 horas, 7 dias, 14 dias, ≤ 35 semanas gestacionais e ≤ 37 semanas gestacionais após a admissão, área sob a curva (AUC) (95% de confiança os valores de intervalo [CI[) foram 0,95 (0,89­1,00), 0,93 (0,86­0,99), 0,91 (0,83­0,98), 0,92 (0,85­0,99), 0,82 (0,69­0,96) e 0,89 (0,80­0,98), respectivamente. No presente estudo, os níveis de IMA e biglican foram maiores e os níveis de decorin menores em mulheres admitidas no hospital com ameaça de trabalho de parto prematuro e que tiveram parto prematuro em 48 horas em comparação com aquelas que deram à luz após 48 horas. CONCLUSãO: Em gestantes admitidas no hospital com ameaça de trabalho de parto prematuro, a predição de parto prematuro do modelo combinado criado pela adição de IMA, decorin e biglican, além da medição do TVS CL, foi maior do que a medição do TVS CL isoladamente. REGISTRO DO ENSAIO CLíNICO: O presente ensaio foi registrado em ClinicalTrials.gov, número NCT04451928.

The effects of 17ß-estradiol plus drospirenone on anthropometric and biochemical measures of adiposity in menopausal women.

PURPOSE: To assess whether there are changes on anthropometric and biochemical measures of adiposity in pre- and postmenopausal women and in the latter before and after 6 months treatment with 17ß-estradiol plus drospirenone. METHODS: Twenty postmenopausal and 20 premenopausal women were enrolled in a prospective comparative study. Postmenopausal women received 1 mg 17ß-estradiol plus 2 mg drospirenone daily for 6 months. Measurements of body mass index (BMI), waist/hip ratio and plasmatic levels of insulin, glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, leptin, adiponectin, orexin-A, glucagon-like peptide-1 (GLP-1) and ghrelin were performed in premenopausal (group 1) and postmenopausal women and in the latter before (group 2a) and after (group 2b) 6 months treatment with 17ß-estradiol plus drospirenone. RESULTS: No significant changes in BMIs, insulin and glucose were observed between group 1 and 2a; and group 2a and 2b. GLP-1 levels were significantly increased in group 1 compared to group 2a (p = 0.035). Leptin levels were significantly increased (p = 0.001) and GLP-1 levels were significantly decreased (p = 0.021) in group 2b compared to group 2a. HDL was significantly decreased while LDL and triglyceride levels were significantly increased in group 2a compared to group 1. (p = 0.030, p = 0.001, p = 0.020; respectively) LDL was significantly decreased (p = 0.010) in group 2b compared to group 2a. GLP-1 had a positive correlation with orexin-A (p < 0.001, r = 0.520) and negative correlation with leptin (p = 0.008, r = -0.345). CONCLUSION: Leptin was significantly higher and GLP-1 was significantly lower in women receiving 17ß-estradiol plus drospirenone treatment. GLP-1 levels were significantly lower after the menopause compared to premenopausal levels. Orexin-A and GLP-1 were positively correlated.

Significance of Cyclooxgenase-2 gene polymorphism and related miRNAs in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. The suppression of cyclooxygenase-2 (COX-2) expression has been known to impair vascular function in endothelial cells; however, the epigenetic factors that cause this are largely obscure. Our aim in this study was to examine the polymorphisms in the gene for COX-2 (PTGS2) and related miRNAs regulating its level in a single-center cohort of patients with PAH. METHOD: In this study, three SNPs and miRNAs (rs5275, rs689470, rs20417, miR-26b-5p, miR-146a-5p, and miR-101-5p) in the PTGS2 were screened in PAH and controls by qPCR. In addition, the COX-2 level was determined by immunoassay to examine the effects of epigenetic factors on its expression levels. RESULTS: The non-dominant genotypes of rs20417 and rs5275 were found to be related to PAH (OR = 8.56, 95% CI = 3.39-21.63, p < 0.0001 and OR = 7.82, 95% CI = 3.30-18.53, p < 0.0001, respectively). We also observed a significant increase in the miR-26b-5p and miR-146a-5p levels in PAH patients (2.18 and 2.35-fold, respectively; for both, p < 0.05). In addition, it was found that SNPs influenced the COX-2, miR-26b-5p, and miR-146a-5p levels in PAH. A negative correlation was also found between COX-2 levels and miR-26b-5p and miR-146a-5p. CONCLUSIONS: As conventional drug therapies may cause lower COX-2 levels, the development of new genetic or epigenetic biomarkers is crucially important for early diagnosis and prognosis. The presence of minor alleles for rs5275 and rs689470 might also be considered as a significant risk factor for developing PAH. Furthermore, locus-specific miRNAs, such as miR-26b-5p and miR-146a-5p, seem to play a critical role in the regulation of PTGS2 expression.

Relationship between serum sialic acid levels and prolidase activity with airflow obstruction in patients with COPD.

ABSTRACT: Our aim in this study was to evaluate the prognostic significance of sialic acid (SA) and prolidase activity and to evaluate the association between airflow obstruction severity and these parameters in chronic obstructive pulmonary disease (COPD) patients.Ninety-four patients (84 M, 10 F) and 34 healthy subjects (19 M, 15 F) were included into the study. COPD staging was performed to COPD patients according to new global initiative for chronic obstructive lung disease criteria which includes pulmonary function tests, symptoms and hospitalization; COPD patients were divided into 4 subgroups as group A (n = 25), group B (n = 19), group C (n = 20), and group D (n = 28).SA and C-reactive protein levels were significantly higher than the control group in all COPD groups. SA levels were significantly higher in group B patients than the control and group A. Prolidase activity was significantly lower than control group in total COPD groups (P < .05). There was a weak negative correlation between SA and forced vital capacity (r = -0.217, P = .038) and forced expiratory volume in 1 second (FEV1) (r = -0.210, P = .045), whereas weak positive correlation was present between SA and Creactive protein (r = 0.247, P = .018) in all patient groups. There was weak positive correlation between prolidase and FEV1 (r = 0.222, P = .033) and FEV1/forced vital capacity (r = 0.230, P = .027).Our study shows that systemic inflammation, prolidase activity, and SA levels in stable COPD patients are associated with airflow obstruction severity. In addition to the prolidase activity; SA levels might be associated with inflammation.

Oxidative lipid, protein, and DNA damage as oxidative stress markers in vascular complications of diabetes mellitus.

PURPOSE: The purpose of this study was to determine the effects of diabetic complications on oxidation of proteins, lipids, and DNA and to investigate the relationship between oxidative damage markers and clinical parameters. METHODS: The study group consisted of 69 type 2 diabetic patients (20 patients without complication, 49 patients with complication) who attended internal medicine outpatient clinics of Istanbul Education and Research Hospital and 19 healthy control subjects. In serum samples of both diabetic patients and healthy subjects, 8-hydroxy-2'deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, N(ε)-(hexanoyl)lysine (HEL) and 15-F2t-iso-prostaglandin (15-F2t-IsoP). as products of lipooxidative damage, advanced oxidation protein products (AOPP), as markers of protein damage, and paraoxonase1 (PON1) as antioxidant were studied. RESULTS: 15-F2t-IsoP (p < 0.005) and AOPP (p < 0.001) levels were significantly higher in diabetic group than control group while there were no significant differences in levels of 8-OHdG and HEL between the two groups. AOPP (p < 0.001) and 8-OHdG (p < 0.001) were significantly higher in diabetic group with complications compared to diabetic group without complications. CONCLUSIONS: Increased formation of free radicals and oxidative stress, under conditions of hyperglycaemia, is one of the probable causes for evolution of complications in diabetes mellitus. Our study supports the hypothesis that oxidant/antioxidant balance is disturbed in diabetic patients.

Evaluation of oxidative stress markers in first trimester for assessment of preeclampsia risk.

AIM: The aim of this study is to determine the predictive values of oxidative stress markers and antioxidants in the development of preeclampsia between 10-14 and also at 20-24 weeks of gestation, after the completion of vascular transformation. MATERIALS AND METHODS: Levels of oxidative stress parameters such as malondialdehyde (MDA), lipidhydroperoxide (LHP) and prostaglandin F(2α) (PGF(2α)), oxidized LDL (oxLDL), and antioxidant status parameters such as paraoxonase 1 (PON1), superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels were measured and compared in 21 preeclamptic and 24 healthy pregnant women. RESULTS: In preeclamptic women, both between 10-14 and also at 20-24 weeks of gestation the levels of oxLDL, MDA and PGF(2α) were significantly higher (P < 0.001, P < 0.001, respectively), PON1, SOD and TAC were significantly lower (P < 0.01, P < 0.001, P < 0.05, respectively) compared to healthy pregnant women; yet there was no significant difference in LHP levels. CONCLUSION: Increased levels of serum MDA and PGF(2α), low levels of SOD and PON1 activity, in 10-14 GW may have been associated with preeclampsia etiology. High levels of MDA and PGF(2α) indicate that the oxidative damage is present well before the clinical symptoms occur. A panel of oxidative stress markers such as MDA and PGF(2α) in maternal blood can predict the development of preeclampsia long before clinical onset.

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.

Circulating miR-155, let-7c, miR-21, and PTEN levels in differential diagnosis and prognosis of idiopathic granulomatous mastitis and breast cancer.

This study investigates whether the circulating miR-155, let-7c, miR-21, and PTEN levels to be used in the differential diagnosis of patients with idiopathic granulomatous mastitis (IGM) and breast cancer (BC). Forty-five patients with BC, 50 patients with IGM, and 48 healthy volunteers were included in the study. Serum miR-21 expression was significantly higher in BC (fold change = 2.42) and IGM group (fold change = 1.33) compared to control (p < .001). Serum miR-155 and let-7c expression levels were significantly lower in both groups compared to the control group (p < .001). miR-21 expression in BC was significantly higher than IGM (fold change = 1.976; p < .001). PTEN levels in BC were significantly higher than IGM (p < .001) and significantly lower than the control group (p < .001); the IGM group was significantly lower than the control group (p < .001). In addition to radiological data, serum miR-21 and PTEN levels may be noninvasive biomarkers that can help differentiate IGM from BC. The results of the study will lead to future studies in the differential diagnosis of IGM and BC.

The effect of nitric oxide, endothelial nitric oxide synthetase, and asymmetric dimethylarginine in hemorrhoidal disease.

AIM: The aim of this study was to examine the roles of nitric oxide (NOx), endothelial nitric oxide synthetase (eNOS), and asymmetric dimethylarginine (ADMA), which is the major endogenous inhibitor of nitric oxide synthases (NOS), in the pathophysiology of hemorrhoidal disease. METHODS: This study included 54 patients with grades 3 and 4 internal hemorrhoidal disease and 54 patients without the disease who attended the General Surgery Clinic. NOx, eNOS, and ADMA levels were measured with the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. RESULTS: The patients had higher NO and eNOS levels and lower ADMA levels than the control subjects (p<0.001). A significant highly positive correlation was found between NO and eNOS (p<0.001). Nevertheless, there was a highly negative correlation between ADMA and NO-eNOS(p<0.001, p<0.001). CONCLUSION: This preliminary study reveals that higher NOx and eNOS activities and lower ADMA levels in the rectal mucosa are observed in patients with hemorrhoidal disease than in those with normal rectal tissue. The imbalance between endothelium-derived relaxing factors, such as NO and endogenous competitive inhibitor of NOS, ADMA, may cause hemorrhoidal disease. Our study proposes that hemorrhoids display apparent vascular dilatation and present with bleeding or swelling. ADMA is an effective NOS inhibitor and may be a promising therapeutic option for hemorrhoidal disease.

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.