Receptor Activator of Nuclear Factor κ-Β Ligand/Osteoprotegerin Axis in Adults with Hb S/ß-Thalassemia and ß-Thalassemia Trait.

There is not enough data about osteoporosis and the role of receptor activator of nuclear factor κ-Β ligand (RANKL)/serum osteoprotegerin (OPG) system in patients with double heterozygosity for sickle cell disease and ß-thalassemia [Hb S (HBB: c.20A>T)/ß-thal] and ß-thal trait. Aim of the study was to investigate bone mineral densities (BMD) and the role of RANKL/OPG system in these cases. We studied 58 adults with Hb S/ß-thal, 52 adults with ß-thal trait, 34 healthy subjects as a control group. The BMD was determined by dual-energy X-ray absorptiometry (DEXA). Biochemical markers of bone metabolism (serum calcium, phosphorus, alkaline phosphatase, osteocalcin) parameters that affect bone metabolism (serum parathyroid hormone, thyroid-stimulating hormone, 25-hydroxyvitamin D, OPG, soluble RANKL [sRANKL]) were studied. Femoral neck Z-scores of 93.2% for ß-thal trait, 83.0% for Hb S/ß-thal patients were within the expected range. Lumbar spine Z-scores of 89.1% for ß-thal, 90.2% for Hb S/ß-thal patients were above -2.0 SD. Z-scores of the control group were within the expected range. Median serum sRANKL level was 2.80, 4.52, 5.79 pmol/L in Hb S/ß-thal, ß-thal trait, control groups, respectively (p = 0.010). Median serum OPG level was 1.07, 0.86, 0.86 pmol/L in Hb S/ß-thal, ß-thal trait, control groups, respectively (p < 0.001). ß-Thalassemia trait alone is not a risk factor for osteopenia/osteoporosis and osteoporosis does not develop in premenopausal women and men younger than 50 years with Hb S/ß-thal. However, as we determined lower levels of osteocalcin, compensatory decrease of sRANKL with compensatory increase of OPG, more severe osteoporosis may develop in advanced ages in these patient populations.

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.

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.

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.

Diagnostic value of microRNAs in prostate cancer patients with prostate specific antigen (PSA) levels between 2, and 10 ng/mL.

OBJECTIVE: Prostate specific antigen (PSA), used for the early diagnosis of prostate cancer (PCa), is one of the best tumour markers known so far. However, in situations when PSA is between 2-10 ng/mL, which is named as grey zone, PSA falls short of distinguishing benign prostate diseases from PCa. On the other hand, it was demonstrated in many previous studies that microRNA (miRNA) could be a marker for cancer. Therefore, in this study, it was aimed to enhance the diagnostic power of PSA, especially with grey zone patients, by the use of miRNA. MATERIAL AND METHODS: Ninety-four patients included in the study were divided into three groups as "control group" (n=44, PSA=2-10 ng/mL and benign), "PCa 1 group" (n=37, PSA=2-10 ng/mL), and "PCa 2 group" (n=13, PSA >10 ng/mL), according to their pathological results and PSA levels. Free PSA (fPSA) and total PSA (T-PSA) levels were measured with chemiluminometric sandwich immunoassay method. Expressions of miRNAs were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) method. The most appropriate specificity, sensitivity and prediction values were found by drawing the receiver operating characteristic (ROC) curves of total PSA, free/total PSA (f/T PSA) ratio, and miRNAs, and the diagnostic powers were compared with each other. RESULTS: Diagnostic powers of the f/T PSA ratio and miRNA were compared in PCa 1 and the control groups to determine the marker with higher area under the curve (AUC). It was shown that the diagnostic power of the combination of miR-16-5p and f/T PSA was higher than that obtained when they were used separately. CONCLUSION: As a result, while making the the discrimination between benign and malignant prostate in patients with grey zone, it was determined that the combination of miR-16-5p and f/T PSA was more valuable than T-PSA or f/T PSA alone. It was thought that diagnostic role of miRNAs in the early diagnosis of the different stages of PCa needed to be examined in further studies with larger groups.

The effects of selective head cooling versus whole-body cooling on some neural and inflammatory biomarkers: a randomized controlled pilot study.

BACKGROUND: Therapeutic hypothermia (TH) has become standard care in newborns with moderate to severe hypoxic ischemic encephalopathy (HIE), and the 2 most commonly used methods are selective head cooling (SHC) and whole body cooling (WBC). This study aimed to determine if the effects of the 2 methods on some neural and inflammatory biomarkers differ. MATERIALS AND METHODS: This prospective randomized pilot study included newborns delivered after >36 weeks of gestation. SHC or WBC was administered randomly to newborns with moderate to severe HIE that were prescribed TH. The serum interleukin (IL)-1ß, IL-6, neuron-specific enolase (NSE), brain-specific creatine kinase (CK-BB), tumor necrosis factor-alpha (TNF-α), and protein S100 levels, the urine S100B level, and the urine lactate/creatinine (L/C) ratio were evaluated 6 and 72 h after birth. The Bayley Scales of Infant and Toddler Development-III was administered at month 12 for assessment of neurodevelopmental findings. RESULTS: The SHC group included 14 newborns, the WBC group included 10, the mild HIE group included 7, and the control group included 9. All the biomarker levels in the SHC and WBC groups at 6 and 72 h were similar, and all the changes in the biomarker levels between 6 and 72 h were similar in both groups. The serum IL-6 and protein S100 levels at 6 h in the SHC and WBC groups were significantly higher than in the control group. The urine L/C ratio at 6 h in the SHC and WBC groups was significantly higher than in the mild HIE and control groups. The IL-6 level and L/C ratio at 6 and 72 h in the patients that had died or had disability at month 12 were significantly higher than in the patients without disability at month 12. CONCLUSION: The effects of SHC and WBC on the biomarkers evaluated did not differ. The urine L/C ratio might be useful for differentiating newborns with moderate and severe HIE from those with mild HIE. Furthermore, the serum IL-6 level and the L/C ratio might be useful for predicting disability and mortality in newborns with HIE.