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.

Prediction of Preterm Delivery Using Serum Ischemia Modified Albumin, Biglycan, and Decorin Levels in Women with Threatened Preterm Labor / Previsão de parto prematuro usando albumina modificada por isquemia sérica, biglicano e níveis de decorina em mulheres com ameaça de trabalho de parto prematuro

Abstract 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.

Resumo 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 (0,89-1,00), 0,93 (0,86-0,99), 0,91 (0,83-0,98), 0,92 (0,85-0,99), 0,82 (0,69-0,96) e 0,89 (0,80-0,98), 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.

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.

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 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.

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.

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.

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.

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.

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.

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

SUMMARY 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.

RESUMO OBJETIVO O objetivo deste estudo foi examinar os papéis do óxido nítrico (NOx), do óxido nítrico sintetase endotelial (eNOS) e da dimetilarginina assimétrica (ADMA), que é o principal inibidor endógeno das óxido nítrico sintase (NOS) na fisiopatologia da doença hemorróida. MÉTODOS Este estudo incluiu 54 pacientes com doença hemorróida interna de grau 3 e 4 e 54 pacientes sem a doença que se inscreveram na Clínica Geral de Cirurgia. Os níveis de NOx, eNOS e ADMA foram medidos com o método de Ensaio Imuno absorvente ligado a enzima (ELISA). RESULTADOS Os pacientes têm níveis mais altos de NO e eNOS e níveis mais baixos de ADMA do que os indivíduos controle (p <0,001). Uma correlação altamente positiva significativa foi encontrada entre o NO-eNOS (p <0,001). No entanto, houve uma correlação negativa muito séria entre ADMA e NO-eNOS (p <0,001, p <0,001). CONCLUSÃO Este estudo preliminar revela que os pacientes com doença hemorróida têm atividades mais altas de NOx e eNOS e níveis mais baixos de ADMA na mucosa retal do que os pacientes com tecido retal normal. Desequilíbrio entre o fator relaxante derivado do endotélio, como; O NO e o inibidor competitivo endógeno da NOS, ADMA, podem causar doenças hemorróidas. Nosso estudo propõe que as hemorróidas exibam aparente dilatação vascular e apresentam sangramento ou inchaço, a ADMA é um inibidor eficaz da NOS e pode ser uma opção terapêutica promissora para a doença hemorróida.

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.

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.

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.

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.

Effects of Quercetin on Lipid and Protein Damage in the Liver of Streptozotocin-Induced Experimental Diabetic Rats.

Quercetin (QR) is part of a subclass of flavonoids called flavonols. We aimed to investigate the effect of QR on malondialdehyde (MDA), advanced oxidation protein products (AOPPs), and glutathione peroxidase (GSH-Px) activity in the liver of diabetic rats. We compared four groups of male adult Wistar albino rats: a control group, an untreated diabetic group, diabetic groups treated with QR, and QR group. Diabetes was induced by a single injection of streptozotocin (STZ) (50 mg/kg). Animals were kept in standard condition. On the 31st day of the study, the liver tissue was removed for biochemical parameters and histopathological evaluations. In an untreated diabetic group, liver MDA and AOPP levels were significantly higher than all groups. QR treatment significantly decreased the increased MDA, AOPP levels, and increased the decreased GSH-Px enzyme activity in liver tissues. The QR-treated rats in the diabetic group showed an improved histological appearance. Lesser vesicular vacuolization and fibrotic areas were observed in the QR-treated diabetic group than in the diabetic group. The STZ-induced liver injury is associated with oxidative stress, and coadministration of QR may reduce this damage effectively in a rat model. Our results are also supported by morphological improvement in liver tissue. Therefore, we think QR may be effective in treating hyperglycemia and oxidative damage in diabetes.