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.

[Comparison of Real Time PCR Cycle Threshold Values in Symptomatic and Asymptomatic COVID-19 Patients]. / Semptomatik ve Asemptomatik COVID-19 Hastalarinda Gerçek Zamanli PCR Döngü Esik Degerlerinin Karsilastirilmasi.

Patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) show different clinical courses ranging from asymptomatic to severe infection requiring intensive care treatment and death. Real-time reverse transcription polymerase chain reaction (rRT-PCR), used in the diagnosis, screening and surveillance of coronavirus-2019 (COVID-19), provides the viral load as a cycle threshold (Ct) value. It has been reported that the Ct value may be related to the course of the infection and the clinical condition of the patient. In this study, it was aimed to compare the Ct and C reactive-protein (CRP) results of symptomatic and asymptomatic patients who were found to be positive with rRT-PCR. Between 14 April and 29 August 2020, a total of 355 patients aged 18 years and older with positive SARS-CoV-2 rRT-PCR test were included in the study. The COVID-19 rRT-PCR test was performed with Bio-speedy SARS-CoV-2 rRT-PCR kit (Bioeksen, Turkey) versions, the kit targeting the RdRp gene region, and the dual gene kit versions targeting the N and ORF1ab gene regions were used. Patients were classified as symptomatic and asymptomatic according to their clinical findings. Ct and CRP results of the patients were analyzed statistically. Of the 355 patients included in the study, 237 (66.7%) were symptomatic and 118 (33.2%) were asymptomatic patients. The mean age of symptomatic patients (46.68 ± 18.03) was observed significantly higher than asymptomatic patients (38.27 ± 13.82) (p<0.001). When the patients are evaluated according to the age groups, the rate of asymptomatic patients was significantly higher in the 21-39 age group, while the rate of symptomatic patients was significantly higher in 65 years and older group (p<0.05). The rate of comorbidity was significantly higher in symptomatic patients (n= 69, 29.1%) than in asymptomatic patients (n= 11, 9.3%) (p<0.001). Hypertension (12.2%), diabetes mellitus (9.7%), chronic respiratory disease (9.3%) and cardiovascular diseases (5.5%) were the most common diseases in symptomatic patients. However, among these, hypertension and chronic respiratory disease were found significantly higher in symptomatic patients (p<0.05). Increased CRP rate in symptomatic patients (64.6%) was found significantly higher than asymptomatic patients (27.3%) (p<0.001). The median of Ct value was found significantly higher in asymptomatic patients (26.34, IQR= 19.78-35.48), than in symptomatic patients (21.77, IQR= 17.81-26.51) (p<0.001). Regarding the medians of Ct values obtained from target genes; RdRp gene Ct value was found significantly higher in asymptomatic patients than in symptomatic patients (p<0.001). However, no statistical difference was found between symptomatic and asymptomatic patients in the ORF1ab and N genes Ct value medians (p> 0.05). As a result, it was observed that SARS-CoV-2 PCR positive patients were symptomatic in the presence of advanced age and comorbidity. Increased CRP value at the time of admission to the hospital was found significantly higher in symptomatic patients. Ct value has been shown to be lower in symptomatic patients, as expected. Although Ct and CRP values are thought to be useful in monitoring the clinical course and prognosis of patients with COVID-19, more detailed studies are needed to prove their clinical value.

Investigation of possible effects of microRNAs involved in regulation of lipid metabolism in the pathogenesis of atherosclerosis.

Due to being stable in the circulatory system plasma miRNAs have been detected in various diseases including coronary artery disease (CAD) which is the major cause of mortality and morbidity worldwide. Atherosclerosis is the major cause of CAD. The first and most important event in the progression of atherosclerosis is endothelial dysfunction and accumulation of the lipids in the arterial wall. Recent studies have shown that different expression levels of lipid metabolism-related miRNAs associated with the pathogenesis of atherosclerosis. Therefore, in this current study, we aimed to investigate the possible effects of lipid metabolism-related miRNAs in plasma of patients with CAD. miRNA analysis was performed by high throughput quantitative PCR method using RNA samples isolated from 46 patients with CAD and 43 non-CAD or control. Data were analyzed using SPSS software version 17 and GeneGlobe Data Analysis Center by Qiagen. Among 40 miRNAs, 4 miRNAs were markedly up-regulated while 4 miRNAs were down-regulated in patients with CAD compared to the control group. The results have shown that, hsa-mir-144-3p, hsa-miR-222-5p and hsa-miR-133a-5p were statistically different in the patient with CAD compared to the control (p = 0.040, 0.030 and 0.005 respectively). Increased expression of hsa-mir-144-3p, hsa-miR-222-5p and hsa-miR-133a-5p would have associated with presence of the CAD. Furthermore, we suggested that these miRNAs might have been useful markers for early detection of the CAD.

Assessment of miR-182, miR-183, miR-184, and miR-221 Expressions in Primary Pterygium and Comparison With the Normal Conjunctiva.

OBJECTIVES: The aim of this study was to investigate the expression levels of miR-126-3p, miR-182-5p, miR-183-5p, miR-184, miR-221-3p, and miR-205-5p in primary pterygium tissue and compare these levels with those in healthy conjunctiva tissue. METHODS: Twenty-four patients who were diagnosed with grade 3 primary pterygium and scheduled for surgery between January 2014 and January 2016 and had no systemic disease or other ocular pathology were included in the study. The control group comprised nasal interpalpebral conjunctival tissue specimens from 24 age- and sex-matched patients with no history of systemic disease or ocular pathology other than cataract. Expression levels of miR-126-3p, miR-182-5p, miR-183-5p, miR-184, miR-221-3p, and miR-205-5p were determined and compared between the pterygium and conjunctiva specimens. RESULTS: Expression levels of miR-182-5p, miR-183-5p, and miR-184 were significantly higher in pterygium tissue compared with normal conjunctival specimens (P<0.0001, P=0.01, and P=0.01, respectively), whereas expression of miR-221-3p was significantly lower (P=0.02). Expression levels of miR-126-3p and miR-205-5p did not differ significantly between the 2 groups (P>0.05). CONCLUSIONS: Expression levels of miR-182-5p, miR-183-5p, and miR-184 are increased, whereas expression of miR-221-3p is decreased in primary pterygium tissue, and these miRNAs may play a role in the pathogenesis of pterygium.

MicroRNA values in children with rheumatic carditis: a preliminary study.

MicroRNAs (miRNAs) are fine regulators of gene expression which participate in the regulation of almost every phase of cell physiology, including development of immune cells and adjustment of immune response. In the studies with in vitro/in vivo model systems, specific miRNAs are revealed to have various roles in cardiovascular development and physiological functions. Furthermore, some studies have been done to understand the role of miRNAs about myocarditis, heart failure and coronary artery diseases. miRNAs crucial role in the pathogenesis of other rheumatic diseases have been investigated, however rheumatic carditis was not studied. The aim of this study is to assess values of miRNAs in children with rheumatic carditis and compare them with healthy children. This study included 36 children with rheumatic carditis (mean aged 12.1 ± 2.1 years) and age-gender matched 35 healthy controls (mean aged 11.1 ± 2.3 years). Conventional echocardiography was performed to all subjects. Using real-time polymerase chain reaction, the expression of some miRNAs (hsamiR-16-5p, hsa-miR-221-3p, hsa-miR-223-3p, hsa-miR-10a-5p, hsa-miR-24-3p, hsamiR-92a-3p, hsa-iR-320a, hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-132-3p, hsamiR-146a-5p, hsa-miR-499a-5p, hsa-miR-1, hsa-miR-125, hsa-miR-196a-5p, hsa-miR-130b-3p, hsa-miR-133b, hsa-miR150-5p,hsa-miR-204-5p, hsa-miR-203a) were analyzed. hsa-miR-16-5p(-1.46 fold, p < 0.01), hsa-miR-223-3p(-1.46 fold, p < 0.01), and hsa-miR-92a-3p(-1.27 fold, p < 0.05) expressions in the patients were lower than those of controls, whereas other examined miRNAs did not differently express between the groups. Results of the study demonstrated that significant downregulation of hsa-miR-16-5p, hsa-miR-223-3p and hsa-miR-92a-3p in children with rheumatic carditis. Since, this is the first study in children with rheumatic carditis, further studies are needed for lightening whether these miRNAs might be helpful as biomarkers.

Seasonal variation of asthma control, lung function tests and allergic inflammation in relation to vitamin D levels: a prospective annual study.

INTRODUCTION: There are scarce data about the role of vitamin D (vitD) in asthma control related to seasons and other confounders. AIM: To investigate the seasonal relationship between vitD levels and asthma control, lung function tests (LFTs) and cytokines during a 1-year period, among 7-17-year-old asthmatic children. MATERIAL AND METHODS: Thirty patients with asthma with house dust mite monosensitization were evaluated 3 monthly about the previous month's health and vitD related lifestyle factors and asthma control test (ACT), spirometry and bronchial provocation test for a year. Serum vitD, vitD binding protein (VDBP), total IgE levels, absolute eosinophil and Treg counts and cytokine levels were simultaneously measured. The seasonal changes of vitD and other parameters and the relationship between 120 pooled data sets of vitD and major outcomes were evaluated. RESULTS: Mean vitD levels, forced expiratory volume in 1 s (FEV1%) and ACT score were lowest in winter and highest in summer. Pooled vitD levels were positively correlated with pooled ACT scores, Treg counts, FEV1% values and VDBP levels and negatively with total immunoglobulin E (IgE) and interleukin-4 (IL-4) levels and bronchodilator response. VitD levels were positively associated with ACT score, and FEV1% value and negatively with serum IgE level and bronchodilator response after adjusting for confounders. CONCLUSIONS: This study revealed that asthma control measures, LFTs and IgE levels were significantly related to serum vitD levels, independent from age, body mass index, inhaled corticosteroid use, sun exposure and season among asthmatic children. Vitamin D levels showed a positive correlation with Treg counts and a negative correlation with Th2 type cytokines.

Evaluation of circulating miRNAs in wet age-related macular degeneration.

PURPOSE: In the present study, we aimed to investigate the changes in plasma miRNA in patients with wet age-related macular degeneration. METHODS: The expression profiles of 384 miRNAs in plasma from 33 patients (22 male, 11 female) who were diagnosed with wet age-related macular degeneration with fundus examination, fundus fluorescein angiography, and optical coherence tomography and 31 controls (17 male, 14 female) were evaluated using high-throughput quantitative real-time PCR. RESULTS: Our results demonstrated that the expression level of five miRNAs (miR-17-5p, miR-20a-5p, miR-24-3p, miR-106a-5p, and miR-223-3p) was significantly upregulated in patients with age-related macular degeneration when compared to the control group (p<0.05). The expression level of 11 miRNAs (miR-21-5p, miR-25-3p, miR-140-3p, miR-146b-5p, miR-192-5p, miR-335-5p, miR-342-3p, miR-374a-5p, miR-410, miR-574-3p, and miR-660-5p) was significantly downregulated in patients (p<0.05). In addition, ten miRNAs (miR-26b-5p, miR-27b-3p, miR-29a-3p, miR-139-3p, miR-212-3p, miR-324-3p, miR-324-5p, miR-532-3p, miR-744-5p, and miR-Let-7c) were expressed only in the patient group. CONCLUSIONS: Our results suggest that plasma miRNA levels may change in wet age-related macular degeneration. These molecules may have an important therapeutic target in patients who are unresponsive to antivascular endothelial growth factor therapy. However, further studies must be conducted for possible effects of miRNAs in vascular disorders of eye such as age-related macular degeneration.

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.

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.

Chronic hepatitis B and IL28B rs12979860 polymorphism: preliminary study.

The aim of this study is to evaluate the role of IL28B rs12979860 polymorphism on pegylated interferon (peg IFN) and oral antiviral treatment in chronic hepatitis B (CHB) patients and to investigate the relationship between the severities of illness with this polymorphism. 74 CHB patients who are received treatment, 61 asymptomatic carriers and 40 healthy controls were recruited in this study. Genomic DNA of controls and patients were extracted from whole blood using High Pure PCR Template Preparation Kit (Roche, Mannheim, Germany) according to the manufacturer's instructions and stored at 4 °C. Genotype distribution of the IL-28B polymorphism at position -3176C/T (rs12979860) (LightMix Kit IL28B, Cat.-No. 40-0588-32 TIB MOLBIOL, Berlin, Germany) was detected by real time PCR (Roche Diagnostics, Manheim, Germany). Thirty of the patients with CHB received peg IFN-α treatment. There were no significant difference between groups by means of age, gender and IL28B rs12979860 polymorphism (p = 0.122, p = 0.07, p = 0.376 respectively). Patients with chronic hepatitis were categorized as grade and stage (minimal, moderate and severe) and then were analyzed for the polymorphism. There was no effect of IL28B -3176 C/T polymorphism on severity of illness (p = 0.293 for grade, p = 0.911 for stage). When the CHB treatment monitored in different time arrivals (beginning, 3th, 6th and 12th months of the treatment) in order to see if there was an effect on virological and biological response none of the genotypes of IL28B -3176C/T polymorphism altered peg IFN or oral antiviral treatment process. There are conflicting results about the role of IL28B rs12979860 polymorphism in CHB in the literature. In this preliminary study, we observed that IL28B rs12979860 polymorphism was not related with severity of illness and also was not effective on treatment response.

Determination of plasma microRNA for early detection of gastric cancer.

Gastric cancer is the fourth most prevalent malignancy worldwide and remains the second most common cause of cancer-related death globally. Understanding the molecular structure of gastric carcinogenesis might identify new diagnostic and therapeutic strategies for this disease. Thus, early detection of gastric cancer is a key measure to reduce the mortality and improve the prognosis of gastric cancer. There have recently been several reports that microRNAs (miRNAs) circulate in highly stable, cell-free forms in blood. Because serum and plasma miRNAs are relatively easy to access, circulating miRNAs also have great potential to serve as non-invasive biomarkers. Although a number of miRNAs associated with gastric cancer have been identified, the underlying mechanism of these miRNAs in tumorigenesis and tumor progression remains to be investigated. The purpose of this study is to identify the potential of serum miRNAs as biomarkers for early detection of gastric cancer patients. RNA was isolated using the High Pure miRNA Isolation Kit (Roche) following the manufacturer's protocol. cDNA and preamplification protocols were obtained from the isolated plasma miRNAs. The BioMark™ 96.96 Dynamic Array (Fluidigm Corporation) for real-time qPCR was used to simultaneously quantite the expression of 740 miRNAs. All statistical analyses were performed using the Biogazelle's qbase PLUS 2.0 software. In this study, among 740 miRNAs that we analyzed only miR-195-5p was significantly (p < 0.05, fold changes = 13, 3) down-regulated in gastric cancer patients compared with control. We demonstrated that miR-195-5p is a novel tumor suppressor miRNA and may contribute to gastric carcinogenesis. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in gastric cancer.

Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?

The aims of this study were to investigate the relationship between magnesium levels and fibromyalgia symptoms and to determine the effect of magnesium citrate treatment on these symptoms. Sixty premenopausal women diagnosed with fibromyalgia according to the ACR criteria and 20 healthy women whose age and weight matched the premenopausal women were evaluated. Pain intensity, pain threshold, the number of tender points, the tender point index, the fibromyalgia impact questionnaire (FIQ), the Beck depression and Beck anxiety scores and patient symptoms were evaluated in all the women. Serum and erythrocyte magnesium levels were also measured. The patients were divided into three groups. The magnesium citrate (300 mg/day) was given to the first group (n = 20), amitriptyline (10 mg/day) was given to the second group (n = 20), and magnesium citrate (300 mg/day) + amitriptyline (10 mg/day) treatment was given to the third group (n = 20). All parameters were reevaluated after the 8 weeks of treatment. The serum and erythrocyte magnesium levels were significantly lower in patients with fibromyalgia than in the controls. Also there was a negative correlation between the magnesium levels and fibromyalgia symptoms. The number of tender points, tender point index, FIQ and Beck depression scores decreased significantly with the magnesium citrate treatment. The combined amitriptyline + magnesium citrate treatment proved effective on all parameters except numbness. Low magnesium levels in the erythrocyte might be an etiologic factor on fibromyalgia symptoms. The magnesium citrate treatment was only effective tender points and the intensity of fibromyalgia. However, it was effective on all parameters when used in combination with amitriptyline.

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.

Affirmative effects of iloprost on apoptosis during ischemia-reperfusion injury in kidney as a distant organ.

OBJECTIVE: Apoptosis and its regulatory mechanisms take part in renal ischemia-reperfusion (I/R) injury which can result in acute renal failure and the inhibition of the caspase is considered as a new therapeutic strategy. In this context, we investigated the antiapoptotic and cytoprotective effects of iloprost, a prostacyclin analog, in kidney as a distant organ. METHODS: Wistar albino rats were randomized into five groups (n = 12 in each) as sham, ischemia, I/R, iloprost (10 µg kg(-1)), and I/R + iloprost (10 µg kg(-1)). A 4 h reperfusion procedure was carried out after 4 h of ischemia. Caspase-8 was evaluated for death receptor-induced pathways, whereas caspase-9 was evaluated for mitochondria-dependent pathways and caspase-3 was investigated for overall apoptosis. Superoxide dismutase (SOD) enzyme activity and nitrite content as an indicator of nitric oxide (NO) production were also analyzed in kidney tissues. RESULTS: Caspases-3, -8, and -9 were all significantly elevated in both ischemia and I/R groups compared to the sham group; however, treatment with iloprost reduced caspases-3, -8, and -9. SOD enzyme activity was attenuated by iloprost when compared to ischemic rats. The different effects of NO were found which change according to the present situation in ischemia, I/R, and treatment with iloprost. CONCLUSIONS: These findings suggested that iloprost prevents apoptosis in both receptor-induced and mitochondria-dependent pathways in renal I/R injury and it may be considered as a cytoprotective agent for apoptosis. Understanding the efficiency of iloprost on the pathways for cell death may lead to an opportunity in the therapeutic approach for renal I/R injury.

Investigation of eNOS G894T Gene Polymorphism in Patients with Pseudoexfoliation Syndrome: A Preliminary Study.

Objectives: The aim of this study is to investigate the relationship between pseudoexfoliation syndrome (XFS) and pseudoexfoliative glaucoma (XFG) and endothelial nitric oxide synthase (eNOS) G894T polymorphism. Methods: Seventy-eight eyes of 78 patients who had undergone uncomplicated cataract surgeries for senile cataract were included in this study. Forty patients with XFS were included in the study group, and 38 patients without XFS constituted the control group. Patients with XFS were divided into two subgroups according to their XFG development, and subgroup analysis was performed. Venous blood samples were taken from all patients before surgery and 894 G>T (rs1799983) polymorphism on the eNOS gene was evaluated by RT-PCR. Results: While the mean age in the control group was 65.97±10.64 years (23 males and 15 females), the mean age in the study group was 73.05±6.79 years (30 males and 10 females), (p<0.001). Regression analysis of the risks caused by the genotype and alleles between the control and study groups revealed that the homozygous alleles were more common in the study group, and heterozygous or mutant alleles have reduced the development of XFS approximately 2-folds. However, this was not statistically significant (p=0.11). Similarly, when subgroup analysis was performed, it was found that there was no significant relationship between XFG in patients with XFS and gene polymorphism. Conclusion: In this study, it was observed that there was no relationship between the G894T polymorphism in the eNOS gene and the development of XFS/XFG.

The plasma microRNA levels and their relationship with the general health and functional status in female patients with fibromyalgia syndrome.

Objectives: The aim of this study was to identify the plasma level of micro-ribonucleic acid (microRNA) expressions and the relationship between plasma microRNA levels with the general health and functional status in female patients with fibromyalgia syndrome (FMS). Patients and methods: Thirty-five female patients (mean age: 42.0±11.8 years; range, 21 to 62 years) diagnosed as FMS and 35 sex-and age-matched healthy controls (mean age: 43.7±8.8 years; range, 21 to 56 years) were enrolled in the study. MicroRNA measurements of the participants in plasma were carried out by using the quantitative polymerase chain reaction (qPCR). A total of 11 plasma levels of microRNA expressions were examined in both groups. The general health and functional status of the patients and controls were assessed by the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form-36 (SF-36) scale. Results: No significant difference was observed between the plasma levels of microRNA expressions in patients with FMS and healthy controls. The plasma level of miR-320a expression was found to be negatively correlated with the total FIQ score in female patients with FMS (p=0.05, r=-0.34). Negative correlations were also detected between the plasma level of miR-320a and miR-320b expressions and the subscale score of SF-36 physical function in female patients with FMS (p=0.01, r=-0.43 and p=0.01, r=-0.43, respectively). A strong positive correlation was found between miR-142-3p and the subscale score of SF-36 mental symptom score in female patients with FMS (p<0.001, r=1.00). Conclusion: The expression levels of microRNAs in plasma between female patients with FMS and controls were not significantly different. Only plasma levels of miR-320a, miR-320b, and miR-142-3p expressions were associated with the general health, functional status, and mental symptom score in female patients with FMS.

ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer.

Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion. We demonstrated that miR-22-3p reduces eukaryotic elongation factor 2 kinase (eEF2K) expression by directly binding to the 3' untranslated region of eEF2K mRNA. Inhibition of EF2K expression recapitulated the effects of miR-22-3p on TNBC cell proliferation, motility, invasion, and suppression of phosphatidylinositol 3-kinase/Akt and Src signaling. Systemic administration of miR-22-3p in single-lipid nanoparticles significantly suppressed tumor growth in orthotopic MDA-MB-231 and MDA-MB-436 TNBC models. Evaluation of the tumor response, following miR-22-3p therapy in these models using a novel mathematical model factoring in various in vivo parameters, demonstrated that the therapy is highly effective against TNBC. These findings suggest that miR-22-3p functions as a tumor suppressor by targeting clinically significant oncogenic pathways and that miR-22-3p loss contributes to TNBC growth and progression. The restoration of miR-22-3p expression is a potential novel noncoding RNA-based therapy for TNBC.

Leptin, visfatin, insulin resistance, and body composition change in chronic obstructive pulmonary disease.

OBJECTIVE: The aim of the study was to compare endocrine parameters such as leptin, visfatin, insulin resistance, exercise capacity and body composition change, the pulmonary functions test (PFT) and arterial blood gases (ABG) parameters of chronic obstructive pulmonary disease (COPD) patients and in healthy controls. MATERIALS AND METHOD: Fifty-five patients with COPD and without malnutrition and 25 healthy controls were included in our study. The serum leptin, visfatin, tumor necrosis factor alpha (TNF-alpha) and insulin resistance, body fat-free mass (FFM) and fat mass (FM) were measured in the groups. Additionally, body mass index (BMI) was calculated and the 6-minute walk test (6MWT), PFT and ABG analyses were performed in all of the cases. RESULTS: No difference in BMI between the COPD group and controls was determined. Serum leptin and visfatin levels, FFM and 6MWT distance were significantly lower in the patients with COPD (p < 0.001, p = 0.001, p = 0.032, p < 0.001, respectively). A correlation was found between serum leptin levels and BMI (r = 0.333, p = 0.027), and with FM (r = 0.365, p = 0.029). Serum visfatin level was correlated with the percentage of forced expiratory volume in the first second in the patients with COPD (r = 0.371, p = 0.013). HOMA-IR (Homeostasis model assessment of insulin resistance) and serum TNF-alpha levels in the patients with COPD were found to be significantly higher than controls (p = 0.001, p < 0.001). CONCLUSION: These results may be earlier signs for further diseases that can emerge in the advanced stages in patients with COPD. Evaluating the patients not only with the pulmonary function and also systemically, contributes to minimizing the mortality and morbidity.

The glutathione-S-transferase gene polymorphisms (Gstt1, Gstm1, and Gstp1) in patients with non-allergic nasal polyposis.

There is an ongoing dilemma about the pathogenesis of nasal polyp (NP). The etiology of NP is multifactorial. Reactive oxygen species and oxidative stress are also suggested to be among the possible factors in NP development. Glutathione-S-transferase (GST) is one of the important detoxifying enzymes. It is not known whether GST plays any role in NP development. We aimed to investigate the relationship between GST subgroup (GSTT1, GSTM1, and GSTP1) polymorphisms, and NP development. Seventy-five patients with NP with or without asthma (NP with asthma: 22, NP without asthma: 53) were used as a study group. As much as 167 healthy individuals were involved as the control group. NP diagnosis was made by nasal endoscopy and paranasal sinus computed tomography (CT). NP was defined as the presence of endoscopically visible bilateral polyps originated from the middle meatus to the nasal cavity and affecting more than one paranasal sinus confirmed by CT. Blood was collected in EDTA-containing tubes and DNA was extracted from the leukocytes. The genotyping of polymorphisms of GSTT1, GSTM1, and GSTP1 were done using real time polymerase chain reaction. Chi-square (chi(2)) and Fisher's (F) exact tests were used for statistical evaluation. A 2-fold increased risk of NP could be found in individuals with the GSTT1 null genotype (OR = 2.03, 95% CI = 1.03-4.011). The distribution of GSTM1 null genotypes was not significantly different between the NP patients and controls and there was also no significance between the GSTP1 genotypes and NP. In conclusion, GST gene polymorphisms may be important in pathogenesis of NP. Additional studies which include larger study groups in different geographic localizations may be more useful to evaluate association with GST polymorphism and NP.