👤 Suat Erdogan

Nerve Guidance Conduits (NGCs) are crucial for reducing trauma during nerve repair, directing axonal growth, and preventing scar tissue formation. In this study, tubular functional NGCs were developed based on vertically aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers (vNGC). They were functionalized by conjugating them with bioactive mimetic peptides: a laminin-derived peptide (LD-BP) to promote vascularization, and nerve growth factor (NGF-BP) and brain-derived neurotrophic factor (BDNF-BP) mimetic peptides to support neural differentiation. The vascular differentiation of HUVECs in response to LD-BP, and the neuronal differentiation of PC12 cells in response to NGF-BP and BDNF-BP, were assessed. The results demonstrated that this approach enabled the fabrication of tubular vNGCs with various diameters, and that vertically aligned PLGA nanofibers significantly improved their structural integrity. Furthermore, BP-conjugated vNGCs outperformed non-conjugated control groups in promoting both vascular and neural differentiation. Importantly, peptide conjugation did not induce cytotoxicity or significantly alter the biodegradability of the vNGCs, supporting their suitability for biomedical applications. Finally, bifunctional vNGCs (BiF-vNGCs), conjugated with LD-BP, NGF-BP, and BDNF-BP, were tested in a rat model of sciatic nerve injury. The BiF-vNGCs showed superior performance compared to unmodified vNGC, Control and s-Control groups, effectively promoting vascularization and neural regeneration in vivo, offering a viable alternative to conventional nerve regeneration methods. Show less

Radiation-induced brain injury causes significant neurotoxicity and cognitive dysfunction in patients undergoing radiotherapy for brain tumors. This study aimed to evaluate the neuroprotective effects of intranasal ketamine on radiation-induced brain injury, specifically focusing on its modulation of perineuronal networks (PNNs), extracellular matrix components, and neuroinflammation. Eighteen male New Zealand White Rabbits were divided into three groups: normal controls, irradiation (IR) with saline (IR + saline), and IR with ketamine (IR + ketamine). Whole-brain IR (20 Gy) was applied to the IR groups, and ketamine (2 mg/kg/day) was administered intranasally for 15 days. Biochemical markers, including malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), brain-derived neurotrophic factor (BDNF), ADAMTS4, and syndecan-1 levels, were measured. Histopathological analysis of hippocampal and cerebellar regions assessed neuronal survival and astrogliosis. Magnetic resonance spectroscopy (MRS) evaluated lactate and Ketamine administration significantly reduced oxidative stress (MDA) and inflammatory markers (TNF-α) while restoring BDNF levels compared to the IR + saline group. ADAMTS4 and syndecan-1 levels were reduced, changes consistent with PNN-associated extracellular matrix dynamics, but without direct confirmation by core PNN markers such as aggrecan or WFA staining. Histopathology showed increased neuronal survival and decreased reactive astrogliosis in ketamine-treated groups. Intranasal ketamine demonstrates significant neuroprotective effects in a radiation-induced brain injury model by reducing oxidative stress and inflammation, modulating extracellular matrix components, and preserving neuronal integrity. These findings highlight ketamine's potential as a therapeutic agent, although direct PNN markers and broader cytokine panels were not assessed. Overall, ketamine showed neuroprotective effects across biochemical, histological, and MRS-supported metabolic readouts. Show less

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

Next-generation sequencing (NGS) has been offered as a large-scale and effective genomic analyzing tool. In this research, we seek to examine the possible benefits of an actionable mutation panel in association with clinical and pathological features in the treatment of esophageal cancer. In our study, 85 cases whose diagnosis of carcinoma was confirmed histopathologically either by endoscopic biopsy or esophageal surgery between 2010 and 2020 were identified from the hospital database. In formalin-fixed, paraffin-embedded tumor samples, a total of 20 genes of AKT1, ALK, BRAF, DDR, EGFR, ERBB2, ERBB3, ESR1, FGFR1, KIT, KRAS, MAP2K1, MET, NRAS, NTRK, PDGFRA, PIK3CA, PTEN, RICTOR and ROS1 were analyzed via NGS for actionable mutations. Of 85 cases, 47 patients (55.3%) were men and 38 (44.7%) were women, and the mean age of the patients was 58.01±11.45 years. There were substantial distinctions in the variables of pathogenicity of variant, operation type, stage, and both lymphovascular and perineural invasion (p<0.05). Most of the primary tumors were situated in the lower thoracic esophagus (n=23; 27%). PIK3CA variant was the highest in number among the variant types (n=17) and was detected in 41.2% of the lower thoracic tumors. The increases in mutation numbers of >2 were especially concentrated in the lower thoracic esophageal carcinomas. The utility of an actionable multigene panel revealed the value of a well-designed NGS workflow in the practical use of clinical outcomes via the prediction of responsiveness to therapeutic agents or indications for novel treatment modalities in addition to the estimation of prognosis. Show less

The main characteristic of proliferative vitreoretinopathy (PVR) is migration, adhesion, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE). Eupatilin is a naturally occurring flavone that has the potential to inhibit cell proliferation and EMT. However, its efficacy on the PVR model induced by transforming growth factor-2 (TGF-β2) is unknown. In this study, the potential effect of eupatilin on proliferation and EMT in the treatment of RPE was investigated. Serum starved human RPE cells (ARPE-19) were treated with 10 ng/ml TGF-β2 alone or co-treated with 25 μM eupatilin for 48 h. Quantitative real-time PCR and Western blot analysis were used to assess targets at the mRNA and protein expression level, respectively. Apoptosis and cell cycle progression was assessed by image-based cytometry. The effect of treatment on cell migration was evaluated by wound healing assay. Eupatilin inhibited TGF-β2-induced RPE cell proliferation via regulating the cell cycle and inducing apoptosis. TGF-β2 upregulated mRNA expression of mesenchymal markers fibronectin and vimentin was significantly downregulated by the treatment, while the epithelial markers E-cadherin and occludin expression was upregulated. The therapy significantly suppressed TGF-β2 encouraged cell migration through downregulating the expression of transcription factors Twist, Snail, and ZEB1 induced by TGF-β2. Furthermore, eupatilin significantly inhibited the expression of MMP-1, -7, and -9, and suppressed NF-κB signalling. These results suggest that eupatilin could inhibit the proliferation and transformation into fibroblast-like cells of RPE cells; thus the agent may be a potential therapeutic value in treating PVR. Show less

Retinoblastoma (Rb) is the most prevalent intraocular pediatric malignancy of the retina. Significant genetic factors are known to have a role in the development of Rb. Here, we report the mutation status of 4813 clinically significant genes in six patients with noncarrier of RB1 gene mutation and having normal RB1 promoter methylation from three families having higher risk for developing Rb in the study. A total of 27 variants were detected in the study. Heterozygous missense variants c.1162G > A (p.Gly388Arg) in the FGFR4 gene; c.559C > T (p.Pro187Ser) in the NQO1 gene were identified. The family based evaluation of the variants showed that the variant, c.714T > G (p.Tyr238Ter), in the CLEC7A gene in first family; the variant, c.55C > T (p.Arg19Ter), in the APOC3 gene and the variant, c.1171C > T (p.Gln391Ter), in the MUTYH gene in second family; and the variant, c.211G > A (p.Gly71Arg), in the UGT1A1 gene in the third family, were found statistically significant (p < 0.05). This study might be an important report on emphazing the mutational status of other genes in patients without RB1 gene mutations and having high risk for developing Rb. The study also indicates the interaction between the retinoic acid pathway and Rb oncogenesis for the first time. Show less