Is Bioavailable Vitamin D Better Than Total Vitamin D to Evaluate Vitamin D Status in Obese Children?

Introduction: Free hormones are biologically more active in target tissues. Thus, measurement of vitamin D taking into account bioavailability and free vitamin D may be preferable, especially when evidence is contradictory, as in obese children. In order to assess bioavailablity and free vitamin D, using a previously reported formula, vitamin D-binding protein (VDBP) level was measured and VDBP polymorphisms were also evaluated because of variations in binding affinity. Methods: Eighty-four obese and 78 healthy children were included. Anthropometry, calcium, phosphorus, alkaline-phosphatase, parathyroid hormone (PTH), 25 hydroxyvitamin D [25(OH)D], bioavailable-free vitamin D, and VDBP concentration and polymorphism were evaluated in the whole group. Results: Obese girls had significantly higher PTH than normal weight girls (p=0.001). Regardless of gender, obese children had significantly higher concentrations of VDBP (p=0.008) and PTH (p=0.002). When samples taken in winter were analyzed, PTH and VDBP were found to be higher and bioavailable and free vitamin D lower in the obese group. There was no difference in terms of total vitamin D between groups during the winter season. Conclusion: While total, free, and bioavailable vitamin D in the obese group was similar to the control group in autumn, free and bioavailable vitamin D in the winter was lower in the obese than the control group. In addition, PTH was higher in the obese group in both autumn and winter. Therefore, more research is needed to evaluate the variability of free and bioavailable vitamin D according to body habitus, season and the effect any differences may have.

Protective Effects of Contractubex® on Stricture Formation after Experimental Corrosive Esophageal Burns in Rats.

AIM/BACKGROUND: Although many agents have been tested as treatment options for caustic esophageal burn (CEB), none have successfully suppressed the formation of strictures. Thus,the purpose of this study was to determine the efficacy of Contractubex® gel (10% onion extract, 50 U/gr heparin, and 1% allantoin) in stricture preventing after CEB. METHODS: In this study, 24 Wistar-albino rats were divided into 4 groups. CEB was initiated with an instillation of 1 mL of 10% NaOH solution into the an isolated esophageal segment for 3 min. Group C (control) was uninjured and untreated. In Group CEB, was initiated but no treatment was given. In Groups CTX1 and CTX2, the animals received 100 and 200 mg/kg/d, respectively, of Contractubex® for 4 weeks via gavage after CEB was initiated. The stenosis indices (SI), histopathologic damage scores, tissue hydroxyproline (HP) levels, and weights of the rats were taken before the experiment and 4 weeks after the experiment. RESULTS: The Mean SI levels, HP levels, and histopathologic damage scores were statistically lower in Groups CTX1 and CTX2 when compared with Group CEB (p <0.05). The treatment groups increased in weight when compared to Group CEB. The results were similar between Group CTX1 and Group CTX2 (p >0,05); the efficacy of the treatment was not dose-dependent. CONCLUSION: For the first time, Contractubex® was used for its antifibrotic, antioxidant, anti-inflammatory, and wound healing effects to treat caustic esophageal burn in rats. It was effective in reducing stricture formation by decreasing the HP levels and histopathologic damage as well as preventing stenosis and weight gain in the treatment groups.

Ziziphus jujube ameliorated cavernosal oxidative stress and fibrotic processes in cavernous nerve injury-induced erectile dysfunction in a rat model.

The aim of this study was to investigate potential antioxidant and antifibrotic effects of Ziziphus jujube (ZJ) in a cavernosal nerve injury (CNI)-induced erectile dysfunction (ED) rat model. Forty-eight male rats were assigned to six-sized groups as group 1: sham-operated; group 2: sham-operated + low-dose ZJ (200 mg/kg); group 3: sham-operated + high-dose ZJ (400 mg/kg); group 4: CNI + distilled water; group 5: CNI + low-dose ZJ; and group 6: CNI + high-dose ZJ. At the end of 2 weeks, intracardiac blood was taken and rats were sacrificed. For biochemical analysis, cavernosal transforming growth factor-beta-1, collagen type I and type 3, fibronectin, α and ß actin were examined in plasma and cavernosa. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and prolidase levels were measured in serum to evaluate antioxidant effect of ZJ. Histopathological examination of tissues revealed that highest fibrosis rate was in group 4 (66.84%). Collagen 1 and 3, alpha and beta actin, fibronectin levels were significantly different among groups (p < .05). Differences between plasma SOD, CAT, MDA and prolidase were also significant among those groups (p < .05). In this study, antioxidant and antifibrotic effects of ZJ were determined in the corporal tissue after CNI. It is thought that ZJ may be beneficial on ED patients especially after radical pelvic surgeries.

The relationship between serum osteopontin and FGF 23 levels with valvular calcification in hemodialysis patients
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BACKGROUNDS AND AIMS: Cardiovascular calcification is an important cause of morbidity and mortality in hemodialysis (HD) patients. Vascular and valvular calcification are indicators of increased tissue calcification. The relationship of osteopontin (OPN) - which is known as a vascular calcification inhibitor - and fibroblast growth factor-23 (FGF-23) - which its related to vascular calcification, as recently shown - to valvular calcification is unknown. In this cross-sectional study, we examined the relationship between heart valve calcification, serum OPN, and FGF-23 levels. MATERIALS AND METHODS: 85 adults who were on HD treatment for at least 6 months were included in the study. Echocardiographic evaluation was made with the General Electric echocardiography device and the same cardiologist. FGF-23 and osteopontin levels were measured by ELISA. RESULTS: 54% of our patients were male, mean age was 49.8 ± 15.1 years, and mean HD duration was 52.5 ± 39.6 months. 34% of the patients were diabetic, and 17.6% had a history of coronary artery disease. 1.25 mmol/L calcium were used as dialysate calcium in 84.7% of the patients. 60% of the patients were on vitamin D replacement therapy, and 7.1% were receiving cinacalcet treatment. Valvular calcification ratio of the patients was 44%. Mean FGF-23 level was 682 ± 771.7 pg/mL, and mean OPN level was 22.2 ± 8.2 ng/mL. When the patients with and without heart valve calcification were compared, the group with heart valve calcification was older and had lower serum OPN levels. There were differences between the groups on left atrial diameters, left ventricular end-diastolic diameters, and posterior-wall thicknesses. In the logistic regression analysis, it was seen that age and serum OPN levels were predictors of valvular calcification. CONCLUSION: Serum osteopontin level is associated with heart valve calcification in HD patients, but there was no relationship found with FGF-23. Further research is needed on the subject.
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miRNA-mediated apoptosis activation through TMEM 48 inhibition in A549 cell line.

Lung has critic function in gas exchange, supplying oxygen to all cells. Rapid metastasis and the high rate of mortality characterises lung cancer. There are two types of this disease, small cell and non-small cell, which differs from each other according to histopathologic features. To date, many therapeutic approaches have been developed to destroy this deadly type of cancer, which one of them is mRNA targeted therapies through miRNA. miRNAs are 19-25 base paired molecules be able to suppress and destruct mRNA and found to be involved in development and progression of lung cancer. Transmembrane Protein 48 (TMEM48) is localised on nuclear pore complex and plays critic roles in nuclear traffic. Known that TMEM48 gene overexpressed in non-small lung cancer cells. Growing TMEM48 suppressed therapeutic studies indicated that decreased TMEM48 level might reveal a therapeutic effect for non-small cell lung cancers. TMEM48 studies based on the same strategy of gene-silencing, however, to our knowledge, any report has been published evaluates TMEM48's regulation by miRNAs. We aimed to clarify if miR-421 might be therapeutic player for non-small cancer cell lines (A549), hereby we suppressed TMEM48 by miR-421 and performed advanced molecular tests. Consequently, we recorded that while miR-421 is significantly suppressing TMEM48 expression; it increased apoptotic and tumor suppressor players CASPASE 3, PTEN and TP53 in A549 line, which is consistent with Annexin V - PI results: 30,6% of A549 observed to be apoptotic - 68,5% of A549 was in GO/G1. Our study indicated that miR-421 can suppress TMEM48 so that leads the cells to apoptosis. But it is not entirely clear how miR-421 triggers apoptosis and whether it interacts with the other cellular death pathways in A549.

Evaluation of serum prolidase activity and oxidative stress markers in men with BPH and prostate cancer.

BACKGROUND: Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are diseases of elderly men and are related to increased oxidative stress (OS). Although prolidase has a role in collagen metabolism, it is also used to evaluate OS in many diseases. However, there is a lack of data about serum prolidase activity (SPA) in prostate cancer. The aim of this study was to evaluate and compare SPA levels in males with BPH and PCa. METHODS: Evaluation was made of a total of 81 men who underwent transrectal ultrasound guided prostate biopsy for a definitive diagnosis due to high PSA levels. Patients were separated into 2 groups as BPH and PCa patients. Pre-biopsy malondialdehyde (MDA), superoxide dismutase (SOD), PSA levels and serum prolidase activities (SPA) were compared between the groups and the correlations of SPA with the other parameters were also investigated in both groups. RESULTS: BPH was diagnosed in 51 patients and PCa in 30. The mean age of patients was similar in both groups as 63.25 ± 5.81 years in the BPH group 65.30 ± 7.35 years in the PCa group(p:0.081). The median MDA and SOD levels were insignificantly increased in the PCa patients. SPA values were similar in BPH and PCa patients. SPA did not correlate with age, PSA, MDA or SOD levels in either group. CONCLUSIONS: Our study results revealed that serum prolidase activity is similar in BPH and PCa cases and is not correlated with MDA, SOD or PSA levels.

Plasma urotensin-2 level and Thr21Met but not Ser89Asn polymorphisms of the urotensin-2 gene are associated with migraines.

BACKGROUND: Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA). METHODS: One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed. RESULTS: Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (ß = 0.508, p = 0.001). CONCLUSION: Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.

CYP gene expressions in obesity-associated metabolic syndrome.

PURPOSE: The contribution of cytochrome P450 (CYP) gene expressions in metabolic syndrome (MetS) has not been elucidated, and was the aim of this study. METHODS: A total of 51 MetS patients and 41 healthy controls with similar age and sex were included to this study. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions using a dynamic array system. RESULTS: We observed marked suppressions in CYP2A6 (p=0.0123), CYP4F2 (p=0.0005), CYP3A5 (p=0.0003), and CYP17A1 (p<0.0001) gene expressions in MetS patients. CONCLUSIONS: This is the first study to provide evidence that depressed expressions of CYP2A6, CYP4F2, CYP3A5, and CYP17A1 genes may play a role in MetS.

Evidence for elevated (LIMK2 and CFL1) and suppressed (ICAM1, EZR, MAP2K2, and NOS3) gene expressions in metabolic syndrome.

The metabolic syndrome (MetS) is a common multicomponent condition including abdominal obesity, dyslipidemia, hypertension, and hyperglycaemia. The aim of this study was to investigate the associations of the expression of a panel of signalling genes with the MetS in a Turkish population. A total of 54 MetS patients and 42 healthy controls with similar age and sex were included to this study. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions using a BioMark 96.96 dynamic array system. We observed marked increases in LIM kinase 2 (LIMK2) and cofilin 1 (CFL1) gene expressions in MetS patients. However, there were significant decreases in intercellular adhesion molecules 1 (ICAM1), ezrin (EZR), mitogen-activated protein kinase kinase 2 (MAP2K2), and nitric oxide synthase 3 (NOS3) gene expressions in MetS patients. Additionally, no marked changes were noted in other 15 genes studied. This is the first study to provide evidence that activation of LIMK2/CFL1 pathway may play an important role in MetS.

The investigation of miR-221-3p and PAK1 gene expressions in breast cancer cell lines.

The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer still remains a major clinical concern. Resistance to tamoxifen is seen in half of the recurrences in breast cancer. The anti-estrogen tamoxifen gains agonistic property by transactivating ERα. PAK1-mediated phosphorylation of serine 305 (S305) of ERα leads to resistance to tamoxifen. In our study, PAK1-induced suggestive tamoxifen resistance was designed. According to our hypothesis, phosphorylation of ERα-S305 by PAK1 may be reversed by PAK1 transcriptional inhibition by miR-221-3p due to miR-221-3p targeting the 3' UTR of PAK1. For this purpose, we used Real-time PCR (qRT-PCR) to measure the expression level of miR-221-3p in ER-positive breast cancer cell lines (ZR-75-1, MCF7) and breast epithelial cell line, hTERT-HME1, as control in the laboratory in our department. The increase in the expression of PAK1 depending on miR-221-3p may be related to ZR-75-1 cell line which has invasive characteristic but other two ER+ cancer cell lines, MCF7 and HCC1500, have milder cancer severity. miR-221-3p may have a role on regulation of PAK1 expression because miR-221-3p expression level decreases while PAK1 expression level increases in SKBR3 cell line. miR-221-3p and PAK1 expressions in MDA-MB-231 cell line are higher than that of hTERT-HME1 cell line. This may mean that miR-221-3p has no regulatory effect on of PAK1 expression in this cell line. According to these results, miR-221-3p may give crucial information about molecular mechanism of the disease upon PAK1 activity or different mechanisms with respect to histopathology and severity of breast cancer.

Expression patterns of miR-221 and its target Caspase-3 in different cancer cell lines.

Caspases are important initiators and most well-known finishers of apoptosis. By changing the death propagation homeostatic equilibrium, their different expression patterns might trigger the progression of hazardous diseases like cancer. miR-221 is an oncogenic miRNA. It is known to have both anti-angiogenic and angiogenic effect. The aim of this work was to compare the expression levels of miR-221 and its target caspase-3 in different cancer cell lines and to find out a relationship between these two. We also tried to establish a prominent relationship between miR-221 and its role in apoptosis by studying their expression levels. Our results indicate that expression of caspase-3 is quite lower as compared to miR-221 expression in all of the selected cancer cell lines. As a result, we conclude that miR-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells. To our knowledge, this is the first study related to the expression levels of caspase-3 and miR-221 in different cell lines at the same time. We expect that our study might pave the way for better understanding the role of miR-221 in apoptotic regulation of caspase-3.