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 Show more
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
Hepatocellular carcinoma (HCC) remains a major health concern, with angiogenesis playing a key role in its progression. Medicinal plants offer valuable anticancer potential. Eremurus spectabilis (ES), Show more
Hepatocellular carcinoma (HCC) remains a major health concern, with angiogenesis playing a key role in its progression. Medicinal plants offer valuable anticancer potential. Eremurus spectabilis (ES), traditionally used in folk medicine, has not been fully explored for its anticancer properties. This study investigates its cytotoxicity on Hep3B cells and its anti-angiogenic activity. E. spectabilis fractions (hexane, chloroform, ethyl acetate, and aqueous ethanol) were obtained from the ethanolic extract. The total phenolic content (TPC) was measured, and the active fractions were analyzed using gas chromatography-mass spectrometry (GC-MS). The xCELLigence Real-Time Cell Analyzer was used to evaluate cytotoxicity against Hep3B cells. Anti-angiogenic activity was assessed using the CAM assay, and docking studies were conducted to predict the mechanism of anti-angiogenesis. ESEA (154.80 ± 0.10 mg/g) had the highest phenolic content, followed by ESC (84.81 ± 6.81 mg/g). Palmitic acid (26%), khusimyl acid (15.9%), glycerol (12.1%), and D-(+)-talofuranose pentakis(trimethylsilyl) ether (9.7%) were the major compounds in ESC, while D-glucopyranose (19.4%), β-D-(+)-talopyranose (15.7%), and D-(-)-tagatofuranose pentakis(trimethylsilyl) ether (13.6%) were among the major compounds in ESEA. All fractions revealed significant cytotoxicity on Hep3B cells, with ESEA (24-h IC E. spectabilis shows a promising dual action for cancer therapy. However, further research is necessary to predict the exact mechanism of action. Show less
Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic o Show more
Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic or likely pathogenic sarcomeric and non-sarcomeric gene mutations and to confirm a final molecular diagnosis in patients diagnosed with hypertrophic cardiomyopathy. A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye. All samples were analyzed with a 17-gene hypertrophic cardiomyopathy panel using next-generation sequencing technology. The gene panel includes ACTC1, DES, FLNC, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, PTPN11, TNNC1, TNNI3, TNNT2, TPM1, and TTR genes. The next-generation sequencing panel identified positive genetic variants (variants of unknown significance, likely pathogenic or pathogenic) in 12 genes for 121 of 392 samples, including sarcomeric gene mutations in 30.4% (119/392) of samples tested, galactosidase alpha variants in 0.5% (2/392) of samples and TTR variant in 0.025% (1/392). The likely pathogenic or pathogenic variants identified in 69 (57.0%) of 121 positive samples yielded a confirmed molecular diagnosis. The diagnostic yield was 17.1% (15.8% for hypertrophic cardiomyopathy variants) for hypertrophic cardiomyopathy and hypertrophic cardiomyopathy phenocopies and 0.5% for Fabry disease. Our study showed that the distribution of genetic mutations, the prevalence of Fabry disease, and TTR amyloidosis in the Turkish population diagnosed with hypertrophic cardiomyopathy were similar to the other populations, but the percentage of sarcomeric gene mutations was slightly lower. Show less