👤 Nazlı Karaca Kurt

Extremely low-frequency (ELF) magnetic fields generated by power-line sources are ubiquitous, yet their long-term effects on neuronal cells remain unclear. We investigated whether continuous exposure (72 - 96 h) to a 60 Hz ELF magnetic field induces oxidative DNA damage and alters cell death pathways in differentiated SH-SY5Y human neuroblastoma cells. Neuron-like cells generated by retinoic acid and brain-derived neurotrophic factor were exposed to 1-3 mT ELF magnetic fields for 96 h, with sham-exposed cells as controls. Chromosomal integrity (Hoechst 33258 staining), apoptosis/necrosis (Annexin V-FITC/propidium iodide flow cytometry), oxidative DNA damage (apurinic/apyrimidinic site analysis), and redox balance (total oxidant and total antioxidant status) were assessed. ELF magnetic field exposure caused intensity dependent nuclear abnormalities, increased oxidative DNA lesions, early oxidative imbalance, and a predominance of necrotic over apoptotic cell death. These findings indicate that continuous low-intensity ELF magnetic field exposure disrupts redox homeostasis and compromises genomic stability in differentiated neuronal cells. Show less

Left ventricular non-compaction (LVNC) can be observed as a phenotypic trait in patients with dilated cardiomyopathy. Familial cases have been increasingly recognized, with sarcomeric gene mutations-particularly in We report a 7-year-old girl with a clinical diagnosis of dilated cardiomyopathy with LVNC since infancy. Genetic analysis revealed two heterozygous missense variants in sarcomeric genes associated with inherited cardiomyopathies: This report highlights the clinical relevance of identifying digenic sarcomeric variants in paediatric cardiomyopathy, particularly when associated with a positive maternal history of PPCM. Familial evaluation and recognition of genotypic overlap may aid in risk stratification and management. Show less

Monogenic obesity, characterized by severe, early-onset obesity due to single-gene defects, often resists traditional weight management strategies. This report presents real-life experiences on the efficacy and safety of setmelanotide, an MC4R agonist, in 4 prepubertal children (ages 3-9) with LEPR and POMC deficiencies. Findings indicate that setmelanotide is effective at lower doses in our patients with POMC deficiency (0.3-0.5 mg/day) than the patients with LEPR deficiency (2.5 mg/day). Treatment was generally well-tolerated, with injection site reactions and hyperpigmentation as common side effects. As novel findings, gonadotropin-related effects such as hypothalamo-pituitary-gonadal axis activation and testicular descent were observed in 2 patients. Growth deceleration was noted in 2 children, and recovery from central hypothyroidism in 1 patient with POMC deficiency. Overall, setmelanotide appears to be effective and well-tolerated in young children with monogenic obesity. However, further studies are necessary to evaluate the long-term effects of early intervention on growth and pubertal development. Show less

Insulin resistance is considered the most important key mechanism in the development of nonalcoholic fatty liver disease (NAFLD). Some studies have reported that hyperinsulinemia decreases the hepatic secretion of apolipoprotein (Apo) B. Chronic hyperinsulinemia in NAFLD may be responsible for the accumulation of triglycerides in hepatocytes. We aimed to investigate whether apolipoproteins are related to histological findings in patients with biopsy-proven NAFLD. We also aimed to evaluate the effects of obesity on apolipoproteins and the pathogenesis of NAFLD. In this cross-sectional study, 91 patients with biopsy-proven NAFLD were included. The control group consisted of 39 healthy subjects who had no history of liver disease or alcohol consumption and were matched for age, gender and smoking. Apoliprotein A1 and Apo B were measured via an immunoturbidimetric method with commercially available OSR6142 Apo A1 and OSR6143 Apo B immunoassay kits on an Olympus AU2700 analyzer. Age, gender, and smoking distribution were similar among nonalcoholic steatohepatitis patients, simple steatosis patients, and controls. The differences in the mean Apo A1 and Apo B levels and the Apo B/A1 ratio among non-alcoholic steatosis, simple steatosis, and control subjects did not reach statistical significance. In addition, patients with obese NAFLD had higher steatosis scores than patients with nonobese NAFLD (p<0.05). Apo A1 and B levels and the B/A1 ratio were not associated with histopathological findings in patients with NAFLD. Fibrosis and ApoB1/A were found to be independent risk factors for metabolic associated fatty liver disease. In addition, obesity increases the grade of hepatic steatosis but does not cause lobular inflammation, ballooning or fibrosis. Show less

To determine the mechanistic roles of oxidative stress, inflammation, and genotoxicity parameters in patients with work-related asthma (WRA) and silicosis. Thirty-eight healthy office workers, 27 employees with a history of exposure and no disease, 24 employees with WRA, and 23 employees with silicosis were included in this study. Superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, and interleukins (IL) 17, 23, and 27 levels were measured in the serum. Genotoxic damage was evaluated by calculating the frequency of micronuclei in swab samples and 8-hydroxy-2'-deoxyguanosine in serum. Serum superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and IL-17, IL-23, and IL-27 levels were found to be statistically significantly higher in the exposure, WRA, and silicosis groups compared with the control group. The frequency of micronuclei in buccal epithelial cells of the patient group was found to be significantly higher than that of the control group. These results may provide information for molecular mechanisms and early diagnosis of WRA and silicosis and will be a guide for taking precautions in the early period. Show less

We report the genetic analysis of a "humanized" hyperlipidemic mouse model for progressive nonalcoholic steatohepatitis (NASH) and fibrosis. Mice carrying transgenes for human apolipoprotein E*3-Leiden and cholesteryl ester transfer protein and fed a "Western" diet were studied on the genetic backgrounds of over 100 inbred mouse strains. The mice developed hepatic inflammation and fibrosis that was highly dependent on genetic background, with vast differences in the degree of fibrosis. Histological analysis showed features characteristic of human NASH, including macrovesicular steatosis, hepatocellular ballooning, inflammatory foci, and pericellular collagen deposition. Time course experiments indicated that while hepatic triglyceride levels increased steadily on the diet, hepatic fibrosis occurred at about 12 weeks. We found that the genetic variation predisposing to NASH and fibrosis differs markedly from that predisposing to simple steatosis, consistent with a multistep model in which distinct genetic factors are involved. Moreover, genome-wide association identified distinct genetic loci contributing to steatosis and NASH. Finally, we used hepatic expression data from the mouse panel and from 68 bariatric surgery patients with normal liver, steatosis, or NASH to identify enriched biological pathways. Conclusion: The pathways showed substantial overlap between our mouse model and the human disease. Show less

Hyperlipidemia is a risk factor for coronary artery disease (CAD). Apolipoprotein A5 (APOA5) is a member of the apolipoprotein APOA1/C3/A4/A5 gene cluster and a major determinant of plasma triglyceride levels in the population. Various studies have identified a number of common (APOA5 c.56C>G; p.S19W; rs 3135506 ) and rare variants in the APOA5 gene in individuals with hypertriglyceridemia. However, little is known on the impact of rare APOA5 mutations for the risk of coronary artery disease; therefore, we screened the APOA5 gene in subjects with CAD. The coding region of the APOA5 gene was screened in 501 subjects (334 with CAD and 167 CAD-free) undergoing diagnostic coronary angiography by denaturing gradient gel electrophoresis. APOA5 p.S19W variant c.56 C>G was found in a total of 61 subjects, five of them homozygous. Beside this well-known mutation, the denaturing gradient gel electrophoresis screening identified only one subject with a synonymous APOA5 mutation, c.70C>A; p.R24R. APOA5 p.S19W was more frequent in patients with CAD (CAD, 14.4%; no CAD, 7.8%; P = 0.021); and in addition, all homozygous subjects (n = 5) for APOA5 p.S19W had CAD. Furthermore, carriers of the p.19W allele had significantly higher triglyceride levels (240 ± 149 vs 185 ± 118 mg/dL; P < 0.01). From these data, we conclude that (1) APOA5 p.S19W is a common variant, with very few additional APOA5 gene mutations; (2) APOA5 p.S19W plays a major role in triglyceride metabolism; and (3) APOA5 p.S19W is a CAD risk factor. Show less