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    Octaarginine functionalized nanoencapsulated system: In vitro and in vivo evaluation of bFGF loaded formulation for wound healing
    (Elsevier, 2022) Erel-Akbaba, Gulsah; Akbaba, Hasan; Keselik, Erdi; Bahceci, Selen Akyol; Senyigit, Zeynep; Temiz, Tijen Kaya
    Despite all treatment efforts, diabetic wounds are still a major health concern that needs to be solved. Growth factor-based therapeutic approaches offer promising results for wound healing therapy. However, their high sensitivity to proteolysis causes repetitive application, and associated high cost makes it necessary to develop an effective delivery system. In this study, an innovative approach for protein delivery was developed and evaluated in terms of wound healing activity. For this purpose, basic fibroblast growth factor was first encapsulated into chitosan and alginate based polymeric system. Then, a cell penetrating peptide, octaarginine, was incorporated onto the system to achieve a higher therapeutic effect. The characterization studies were performed, and the optimal nanoparticle system was dispersed in hydroxypropyl methylcellulose for providing skin application. The in vitro and in vivo efficiency of the system was also evaluated. According to the results, the obtained gel formulation is safe for the applied doses up to 150 mg/mL and significantly promotes fibroblast cell migration in 48 h. Furthermore, in vivo studies revealed that the diabetic wound healing efficiency of basic fibroblast growth factor nanoencapsulated gel system significantly accelerates wound healing. Moreover, by functionalizing this system with octaarginine, epithelization, granulation of tissue formation, and treatment efficacy were promoted. In conclusion, this work designs a suitable cell penetrating peptide functionalized nanoencapsulated system for growth factor delivery, which provides a promising therapeutic potential for hard-to-heal skin lesions, particu-larly diabetic wounds.
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    Prenatal Dexamethasone Exposure in Male Rats Alters Gene Expression Patterns of Epigenetic Enzymes in Hippocampus and Cortex
    (Aves, 2022) Turunc, Ezgi; Uyanikgil, Yigit; Temiz, Tijen Kaya; Yalcin, Ayfer
    Objective: This study aimed to examine the effects of prenatal stress (PS) induced by dexamethasone exposure on gene expression levels of epigenetic enzymes in hippocampus and cerebral cortex of male rats through relative mRNA levels of histone acetyltransferases (activating transcription factor 2, P300), histone deacetylases (HDAC1, HDAC2), and DNA methyltransferases (DNMT1, DNMT3a, DNMT3b). Methods: Pregnant rats were daily injected subcutaneously with dexamethasone (0.2 mg/kg) or saline during the third week of gestation. After birth, male rats were killed at 90 days of age (n = 5 for control and dexamethasone groups). Hippocampal and cortical tissues were used for gene expression analyses. The effects of dexamethasone on epigenetic mechanisms were investigated by real-time polymerase chain reaction through relative mRNA levels of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2. Statistical comparisons were performed with Student's t-test. Results: Prenatal dexamethasone exposure (PDE) caused increased DNMT1, DNMT3a, DNMT3b, activating transcription factor 2 and decreased P300 mRNA levels in hippocampus while increased DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2 mRNA levels were achieved in cortex. Furthermore, no significant differences were obtained in cortical DNMT1 and hippocampal HDAC1 and HDAC2 gene expression levels between control and prenatally stressed rats. Conclusion: Our results emphasize the effect of prenatal dexamethasone exposure on gene expression levels of epigenetic enzymes involved in histone acetylation/deacetylation and DNA methylation in male rats and suggest that prenatal stress may lead to epigenetic dysregulation through alterations in hippocampal and cortical gene expression patterns of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2.