Reduced expression of miRNAs as potential biomarkers in axial spondyloarthritis.

OBJECTIVE: This study aimed to investigate the value of miR-29a-3p, miR-27a, miR126-3p, miR-146a-5p, miR-625-3p, miR-130a, miR-32, miR-218, miR-131, and miR5196 in the diagnosis of axial spondyloarthritis and to determine whether there is a difference in miRNA expression levels between radiographic axial spondyloarthritis and non-radiographic axial spondyloarthritis, as well as the relationship between miRNA expression levels, disease activity, and uveitis history. METHODS: This study included 50 patients with axial spondyloarthritis (25 with radiographic axial spondyloarthritis and 25 with non-radiographic axial spondyloarthritis) and 25 healthy individuals. The fold change of miRNA expression for each miRNA was calculated using the 2-ΔΔCt method. RESULTS: The expression of all miRNAs except miR-130a was downregulated in axial spondyloarthritis patients (miR-27a: fold regulation: -11.21, p<0.001; miR-29a-3p: fold regulation: -2.63, p<0.001; miR-32: fold regulation: -2.94, p=0.002; miR-126-3p: fold regulation -10.94, p<0.001; miR-132: fold regulation: -2.18, p<0.001; miR-146-5p: fold regulation: -9.78, p<0.001; miR-218: fold regulation: -2.65, p<0.001; miR-625-3p: fold regulation: -2.01, p=0.001; miR-5196-3p: fold regulation: -7.04, p<0.001). The expression levels of these miRNAs did not differ significantly between non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis patients (p>0.05 for all). CONCLUSION: Particularly, miR-27a, miR-126-3p, miR-146-5p, and miR-5196-3p were found to be substantially downregulated in both non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis patients, suggesting their potential as diagnostic biomarkers for axial spondyloarthritis.

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

Investigation of the relationship between endothelial nitric oxide synthase T786C polymorphism and PSA, PSA derivatives, and prostate cancer in the Turkish population.

Background: Prostate cancer is a slowly progressing cancer. However, it has remained a major medical problem for affected men. Risk factors of prostate cancer include age, race, and prostate cancer family history. Prostate cancer may occur at different frequencies between ethnic populations and countries. Currently, studies on genetic risk factors in prostate cancer aetiology have been increasing. Due to the importance of changes in endothelial nitric oxide synthase in carcinogenesis, we aimed to reveal whether eNOS T786C polymorphism is associated with prostate cancer. Methods: Archival samples included in this study were whole blood samples taken from patients who were grouped according to prostate biopsy pathology results (BPH, n: 42; PCa, n: 48) and from healthy participants (controls, n:27). DNA was isolated from these whole blood samples and real-time polymerase chain reaction analysis was performed for endothelial nitric oxide synthase T786C polymorphism with LightCycler 480 II. Measured free and total prostate-specific antigen serum levels were evaluated retrospectively. Results: There was a statistical difference between patient-healthy control and control-healthy control groups regarding genotype distributions for eNOS T786C hism. Controls were more likely to have TC and CC genotypes and C alleles than the other two groups. Conclusions: Compared to other groups, the percentage of the eNOS786C allele in the control group was found to be higher. As a result of these data, it can be thought that carrying the allele may be protective against the disease.

Circulating MicroRNAs in the Screening of Prenatal Down Syndrome.

OBJECTIVE: Screening tests are recommended to identify genetic defects, chromosomal aneuploidies, and structural birth defects. Sonographic and maternal serum-based options are available for the risk assessment of aneuploidy in the first and/or second trimester. Also, invasive diagnostic methods, such as amniocentesis, are used for prenatal diagnosis, but these methods carry a tangible risk to the fetus. However, in recent years, circulating fetal nucleic acids have a promising moleculer tool in the noninvasive prenatal diagnosis of fetal chromosomal aneuploidies. In this study, we aimed to explore the usability of microRNAs (miRNAs) in this process of prenatal diagnosis. METHODS: Fourteen pregnant patients who were found to be carrying fetuses with congenital anomalies were designated as the patient group; 16 pregnant women identified as being at risk of carrying children with such anomalies-but whose fetuses were later found to be anomaly-free-were assigned to control group 1; and 13 pregnant women who had been screened and who had not been identified as being at risk made up control group 2. An analysis of miRNA expression, isolated from maternal plasma and amniotic fluid samples, was performed by quantitative real-time polymerase chain reaction. RESULTS: It was found that hsa-miR-629-5p, hsa-miR-320c, hsa-miR-21-5p, hsa-let-7c-5p, hsa-miR-98-5p, hsa-miR-486-5p, hsa-miR-4732-5p, and hsa-miR-181a-5p levels increased in the patient group's maternal plasma compared to that of the control group. CONCLUSION: In light of these data, we believe that miRNAs may have an important role in the noninvasive prenatal diagnosis of fetal birth defects, especially Down syndrome.

Effects of Trans-Cinnamaldehyde on Reperfused Ischemic Skeletal Muscle and the Relationship to Laminin.

PURPOSE: Ischemia-reperfusion (I-R) injury is a serious problem caused by vascular trauma, tourniquet use and/or compartment syndrome. Studies have reported that skeletal muscle function is impaired due to the lower extremity I-R injury. There are insufficient studies on the treatment methods used for the recovery of dysfunction. This study is designed to investigate the effects of trans-cinnamaldehyde (TCA), a volatile oil of cinnamon structure, on the contractile dysfunction due to I-R injury of rat extensor-digitorum-longus (EDL) muscle. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into three groups. Except for the animals in the control group, all animals received saline (3-ml/kg) or TCA solution (30-mg/kg) which was administered orally three times with an 8-h interval before ischemia. After 24-hours, experimental groups were subjected to 3-h of lower extremity ischemia followed by 5-h reperfusion period. Then, the compound muscle action potential (CMAP) and mechanical activity of muscle were recorded using the standard electro-biophysical techniques. RESULTS: There was a decrease in the maximum contractile force in I-R group compared to the control group (p < 0.05). Oxidative damage indicator (MDA) and antioxidant indicator (CAT) increased in the EDL muscle and serum samples in the I-R group (p < 0.05). Laminin expression showed a reduction in the I-R group (p < 0.05). It was seen that TCA achieve again the maximum contraction force in the EDL muscle (p < 0.05) and maintain the expression of laminin (p > 0.05). CONCLUSION: We concluded that TCA has a potential protective effect with antioxidant effects against I-R injury and may maintain laminin levels.

Association between serum adropin levels and isolated coronary artery ectasia in patients with stable angina pectoris.

OBJECTIVE: Dilation of one or more coronary artery segments to a diameter at least 1.5 times that of a normal adjacent segment is referred to as coronary artery ectasia (CAE). Adropin is a protein involved in endothelial function and is shown to have a protective effect on the regulation of cardiac functions. Atherosclerosis and endothelial dysfunction play an important role in the development of CAE. The aim of this study was to investigate the association between serum adropin levels and isolated CAE. METHODS: Patients with stable angina pectoris who underwent coronary angiography (CAG) between August 2017 and July 2018 were evaluated prospectively. A total of 92 subjects were included in the study-40 patients over 18 years old and diagnosed with isolated CAE based on CAG findings and a control group of 52 patients. RESULTS: Serum adropin level was found to be significantly lower in the isolated CAE group compared to the control group (1019.57 pg/mL and 1151.10 pg/mL, respectively, p=0.010). The isolated CAE group also exhibited a significantly higher mean platelet volume than that in the control group (10.75 fL and 10.17 fL, respectively, p=0.011). CONCLUSION: Our results show that there is an association between low serum adropin level and isolated CAE.

Modulation of oxidative-nitrosative stress and inflammatory response by rapamycin in target and distant organs in rats exposed to hindlimb ischemia-reperfusion: the role of mammalian target of rapamycin.

Mammalian target of rapamycin (mTOR) has been recognized with potential immunomodulatory properties playing an important role in various physiopathological processes including ischemia-reperfusion (I/R) injury. I/R injury stimulate reactive oxygen and nitrogen species by activating nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase, respectively. Controversial results have been obtained in different I/R models following localized I/R; however, the precise role of the mTOR signaling pathway remains undefined. The objective of the current study was to evaluate the role of the mTOR in oxidative-nitrosative stress and inflammation in hindlimb I/R-induced injury in target and remote organ injuries. In rats subjected to I/R, an increased expression of ribosomal protein S6 (rpS6), inhibitor κB (IκB)-α, nuclear factor-κB (NF-κB) p65, inducible nitric oxide synthase, cyclooxygenase 2, gp91phox, and levels of tumor necrosis factor α, nitrite, nitrotyrosine, malondialdehyde and the activities of myeloperoxidase and catalase in the tissues and (or) sera were detected. Treatment with rapamycin, a selective inhibitor of mTOR, reversed all the I/R-induced changes as manifested by its anti-inflammatory and antioxidant effects in kidney and gastrocnemius muscle of rats. Collectively, these findings suggest that rapamycin protects against I/R-induced oxidative-nitrosative stress and inflammation leading to organ injuries via suppression of mTOR/IκB-α/NF-κB signaling pathway.

Profiles of Circulating MiRNAs Following Metformin Treatment in Patients with Type 2 Diabetes.

BACKGROUND: Metformin, a widely used biguanide class of anti-diabetic drug, has potential to increase insulin sensitivity and reduce blood glucose to treat type 2 diabetes (T2D). It has been reported that metformin has an activity on regulation of miRNAs by targeting several downstream genes in metabolic pathways. However, molecular mechanism underlying the process is still not fully known. In this study, it was aimed to identify differential expression profiles of plasma derived miRNAs following 3 months metformin treatment in patients with T2D. METHODS: The plasma samples of 47 patients with T2D (received no anti-diabetic treatments) and plasma samples of same 47 patients received 3 months metformin treatment was recruited to the study. Total RNAs were isolated from plasma and reverse transcribed into cDNA. Profiles of differential expressions of miRNAs in plasma were assessed by using of micro-fluidic based multiplex quantitative real time -PCR (BioMarkTM 96.96 Dynamic Array). RESULTS: Our results showed that expression profiles of 13 candidate miRNAs; hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR- 21-5p, hsa-miR-24-3p, hsa-miR-26b-5p, hsa-miR-126-5p, hsa-miR-129-5p, hsa-miR-130b-3p, hsa-miR-146a-5p, hsamiR- 148a-3p, hsa-miR-152-3p, hsa-miR-194-5p, hsa-miR- 99a-5p were found significantly downregulated following metformin treatments in patients with T2D (p<0.05). CONCLUSIONS: In conclusion, our finding could provide development of better and more effective miRNAs based therapeutic strategies against T2D.

Neutrophil gelatinase-associated lipocalin as a screening test in prostate cancer.

OBJECTIVE: Prostate specific antigen (PSA) with digital rectal examination is used for diagnosis of prostate cancer (PCa), where definite diagnosis can only be made by prostate biopsy. Recently neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin family member glycoprotein, come into prominence as a cancer biomarker. This study is aimed to test serum NGAL as a diagnostic biomarker for PCa and discriminate PCa from benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: In this prospective study, 90 patients who underwent transrectal ultrasound-guided 12-core prostate biopsy between May 2015 and September 2015, were evaluated. Histopathologically diagnosed 45 PCa and 45 BPH patients were enrolled in this study. Serum NGAL and PSA levels of all participants were measured, then these data were evaluated by statistical programs. RESULTS: When sensitivity fixed to 80% specificity of NGAL was better than PSA (49%, 31% respectively). Receiver operating characteristic (ROC) curve analysis showed that NGAL alone or its combined use with PSA have better area under curve (AUC) results than PSA alone (0.662, 0.693, and 0.623 respectively). CONCLUSION: In conclusion NGAL gave promising results such as increased sensitivity and a better AUC values in order to distinguish PCa from BPH. NGAL showed a potential to be a non-invasive biomarker which may decrease the number of unnecessary biopsies.

The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children.

BACKGROUND: Recent evidence about the various effects of vitamin D (vit D) on innate and adaptive immunity has led to a search for the role of vit D in asthma. It is postulated that a decrease in cathelicidin, a multifunctional host defense molecule, production due to low vit D status may predispose to infectious complications in children with asthma. OBJECTIVE: The aim of this study was to determine the association of vit D, vit D-binding protein (VDBP) and cathelicidin with acute asthma attacks among children with allergic asthma. METHODS: This prospective study included 35 patients with acute asthma attack and 32 children with controlled asthma, and all were matched by sampling season, sensitization to mites, and previous severity of asthma. A comprehensive questionnaire about risk factors, blood sampling for 25-hydroxyvitamin D vit D, VDBP, and cathelicidin levels; spirometric indices were used. Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis. RESULTS: The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group (p < 0.001). The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma (p = 0.002). There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels. Risk factors that may influence vit D levels revealed that body mass index (BMI) (p = 0.038), duration of sun exposure (p < 0.001), and amount of dietary vit D (p < 0.001) independently affected serum vit D levels. Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks (p < 0.001, adjusted odds ratio 16.11). Cathelicidin levels showed a significant positive association with asthma attacks and BMI. CONCLUSIONS: Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma.

Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats.

PURPOSE: Hypoxic-ischemic brain injury that occurs in the perinatal period is one of the leading causes of mental retardation, visual and auditory impairment, motor defects, epilepsy, cerebral palsy, and death in neonates. The severity of apoptosis that develops after ischemic hypoxia and reperfusion is an indication of brain injury. Thus, it may be possible to prevent or reduce injury with treatments that can be given before the reperfusion period following hypoxia and ischemia. Levetiracetam is a new-generation antiepileptic drug that has begun to be used in the treatment of epilepsy. METHODS: The present study investigated the effects of levetiracetam on neuronal apoptosis with histopathological and biochemical tests in the early period and behavioral experiments in the late period. RESULTS: This study showed histopathologically that levetiracetam reduces the number of apoptotic neurons and has a neuroprotective effect in a neonatal rat model of hypoxic-ischemic brain injury in the early period. On the other hand, we demonstrated that levetiracetam dose dependently improves behavioral performance in the late period. CONCLUSIONS: Based on these results, we believe that one mechanism of levetiracetam's neuroprotective effects is due to increases in glutathione peroxidase and superoxide dismutase enzyme levels. To the best of our knowledge, this study is the first to show the neuroprotective effects of levetiracetam in a neonatal rat model of hypoxic-ischemic brain injury using histopathological, biochemical, and late-period behavioral experiments within the same experimental group.

Prevalence of listeria, Aeromonas, and Vibrio species in fish used for human consumption in Turkey.

A total of 78 raw retail fish samples from 30 freshwater and 48 marine fish were examined for the presence of Listeria, Aeromonas, and Vibrio species. The overall incidence of Listeria spp. was 30% in freshwater samples and 10.4% in marine fish samples. Listeria monocytogenes (44.5%) was the most commonly isolated species in freshwater fish, and Listeria murrayi (83.5%) was the most commonly isolated species in marine fish samples. Motile aeromonads were more common in marine fish samples (93.7%) than in freshwater fish samples (10%). Vibrio alginolyticus, Vibrio fluvialis, and Vibrio damsela were isolated only in marine fish samples, representing 40.9, 38.6, and 36.3% of Vibrio isolates, respectively. In freshwater and marine fish, the highest incidences of Listeria and Aeromonas were found in skin samples; the highest incidence of Vibrio in marine fish was found in gill samples. The location of Listeria spp. and L. monocytogenes in a fish was significantly different among freshwater fish. A high incidence of these bacterial pathogens was found in the brown trout (Salmo trutta) and horse mackerel (Trachurus trachurus). Handling of contaminated fish, cross-contamination, or eating raw fish might pose a health hazard, especially in immunosuppressed individuals, elderly people, and children. This study highlights the importance of bacterial pathogens in fish intended for human consumption, but more study is needed.