👤 Keramettin Uğur Özkan

Prosthetic valve thrombosis (PVT) is a critical and life-threatening condition driven by multifactorial etiologies, including genetic predispositions. The study was designed as a single-center retrospective manner. Echocardiographic features and genetic test including factor II/prothrombin (G20210A), factor V Leiden (G1691A), factor V R2 (A4070G), apolipoprotein (Apo) B-100 (G10708A), ApoE (C112R), ApoE (R158C), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, factor XIII G103T (V34L), β-fibrinogen (455G>A), PAI-1 4G/5G, and HPA-1 GPIIIa (T196C) genotyping variations were assessed. We performed genetic tests on 175 patients with PVT (biologically women [n = 124, 70.9%], with a mean age of 49.8 ± 13.1 years) and 101 patients (biologically women [n = 57, 56.4%], with a mean age of 54.7 ± 13.6 years) without thrombus formation. The thrombosis group was significantly younger compared with controls (p = 0.004). The percentage of patients with mechanical aortic valves was significantly lower in the thrombosis group compared with controls (22.3% vs 34.7%, p = 0.025). A significant difference was observed between the thrombosis and control groups regarding the genotype ratios of factor II/prothrombin (G20210A) (heterozygous, 6.8% vs 1%, p = 0.043) and HPA-1 GPIIIa (T196C) (homozygous mutant, 7.8% vs 0%, p = 0.034). In addition, there was a significant association of heterozygous MTHFR (A1298C) variation with obstructive thrombosis compared with nonobstructive thrombosis (46.9% vs 29.2%, p = 0.046). In conclusion, this is the first study to report a potential association between genetic variants, including HPA-1 GPIIIa (T196C), factor II/prothrombin (G20210A), MTHFR (A1298C), and PVT, necessitating extensive further research and additional clinical consideration. Show less

Neurological disorders represent a significant burden on human health, particularly as global life expectancy continues to rise. Among these conditions, Alzheimer's disease is notably prevalent. Of greater concern, if left untreated or unaddressed, Alzheimer's disease can progress to dementia, leading to severe cognitive decline and a substantial reduction in quality of life. In this study, 15 novel benzofuran-azacyclic hybrids were designed and synthesized. The final compounds were evaluated for their inhibitory potency on AChE and BACE-1 enzymes, and in silico studies were performed to clarify their binding modes. Finally, structure-activity relationships (SARs) were proposed for future studies. The results indicated that the most promising compound is Show less

Genetic and numerous epidemiologic studies have identified lipoprotein (a) [Lp(a)] as a risk factor for atherothrombotic diseases. The structure of Lp(a) is similar to plasminogen and tissue plasminogen activator and it competes with plasminogen for its binding site, leading to reduced fibrinolysis. Furthermore, since Lp(a) stimulates the secretion of plasminogen activator inhibitor-1, it may lead to thrombogenesis. In this cross-sectional study, we aimed to investigate Lp(a) levels in patients with mechanical prosthetic valve thrombosis (MPVT). Blood samples for Lp(a) determination were obtained from 80 MPVT patients (median age: 48.5 (39-59.75) years; 47 male) and 75 age and sex matched controls (median age: 52 (39-63) years; 44 male) with normally functioning mechanical prosthetic valves. The Lp(a) levels in the PVT group were significantly higher than in the controls [22(16.2-39.4) vs. 6.9(2.9-24.6) mg/dL, p < 0.001]. Elevated Lp(a) levels, recent history of subtherapeutic anticoagulation, history of cerebrovascular accidents (CVA) and a low value of international normalized ratio on admission were found to be the independent predictors of PVT. Lp(a) levels above 19.6 mg/dL predicted PVT with a sensitivity of 65% and a specificity of 71% (AUC:0.767; 95%CI: 0.687 to 0.847; p < 0.001). Lp(a) levels were significantly higher in PVT patients with a history of CVA [42.0 (23.6-53.6) vs. 21.1 (16.1- 36.2) mg/dL, p = 0.012]. Elevated Lp(a) levels may be associated with MPVT. The assessment of plasma Lp(a) levels in patients with prosthetic heart valves may provide additive information regarding the risk of PVT and CVA. Show less

Propylene glycol (PG) is incorporated into ruminant diets to boost glucogenic energy availability, yet its precise effects on adipose tissue development remain incompletely defined. The study was designed as a 3 × 3 factorial experiment with two independent variables: dose of PG and duration of fattening. Three groups were formed, including a dose group of PG 1.5 mL/kg live weight (PG1.5), a dose group of PG 3 mL/kg live weight (PG3), and a group without PG (PG0). Gluteal adipose tissues were collected from animals slaughtered on days 60, 90, and 120. mRNA, protein, and fatty acid profiles were analyzed. Protein-protein interaction and gene set enrichment analysis were also performed. On day 60, FABP4 was approximately 3-fold higher at both mRNA and protein levels in PG3 compared to PG0, nearly 2-fold higher at the protein level in PG1.5, and SREBP-1c protein levels were reduced in PG1.5 compared to PG0. On day 120, FABP4, PPARγ, C/EBPα exhibited an increasing trend at both mRNA and protein levels in PG groups, whereas SREBP-1c was decreased in PG3. Fatty acid profiling revealed C16:0, C18:0, and C18:1 comprised over 70% of total lipids. PG supplementation shifted the profile toward unsaturated species, reducing saturated fatty acid proportions and enhancing nutritional indices, particularly in PG1.5. Findings at the bioinformatics levels demonstrate PG exerts clear dose- and time-dependent modulation of adipogenic transcription factors, fatty acid composition, and molecular interaction networks in lamb adipose tissue. Early PG3 feeding elevates FABP4 and suppresses SREBP-1c, whereas prolonged supplementation enhances PPARγ and C/EBPα and drives a favorable shift in lipid profiles. Network and pathway analyses reveal coordinated regulation via NR1H3/RXR and PPAR axes, suggesting PG not only optimizes energy partitioning but also supports cellular homeostasis. These results could contribute to the development of potential strategies aimed at supporting adipose tissue quality and metabolic health in sheep. Show less

In this study, the synthesis of N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives (3a-3k) and to investigate their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase 1 (BACE-1) inhibition activity were aimed. Mass, Show less

This study examines the synthesis and evaluation of 11 newly developed compounds as potential anti-Alzheimer's agents that occur via cholinesterase and β-secretase inhibition. The compounds were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman method. The results showed that several compounds exhibited significant inhibition of AChE, particularly compounds 6d, 7a, and 7e, which demonstrated high inhibitory activity at lower concentrations, with IC Show less

Non-syndromic monogenic obesity is a rare cause of early-onset severe obesity in the childhood period. The aim of this study was to screen four obesity related genes ( Next-generation sequencing of all exons in Fifteen different variants in nineteen patients were identified with a variant detection rate of 12.3%. While six different heterozygous variants were observed in In conclusion, MC4R variants are the most common genetic cause of monogenic early-onset obesity, consistent with the literature. The c.496G>A variant in Show less

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ β-catenin pathway by binding to β-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the β-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ β-catenin pathway in the pathogenesis of colorectal cancer. Show less

We report two newborns with female external genitalia and bilateral inguinal swelling who were diagnosed with 17β-hydroxysteroid dehydrogenase type 3 deficiency, a rare cause of 46,XY disorder of sexual development. The first case had normal clitoral size and vaginal and urethral openings, palpable gonads in the inguinal region, low testosterone, and low levels of basal and GNRH-stimulated gonadotropin. The second case had similar external genitalia, low testosterone but borderline basal and normal stimulated gonadotropin levels. Low testosterone/androstenedione ratios (0.22 and 0.24, respectively; normal, >0.8) after human chorionic gonadotropin stimulation indicated 17β-hydroxysteroid dehydrogenase type 3 deficiency. HSD17B3 sequencing revealed a homozygous novel mutation (c.464A>C, p.H155P) in exon 6 in the first case and homozygous c.239G>A (p.R80Q) in exon 3 in the second. Show less