Peripheral nerve injuries often lead to significant functional impairment. While autografts remain the gold standard for repairing critical-sized nerve defects, donor site morbidity and limited graft Show more
Peripheral nerve injuries often lead to significant functional impairment. While autografts remain the gold standard for repairing critical-sized nerve defects, donor site morbidity and limited graft availability have prompted the exploration of alternative strategies. Although studies investigating nerve regeneration using nerve conduits and biological agents are present in the literature, research investigating the effect of neurotrophic factors enriched secretome with biocompatible 3D conduits combination is insufficient. The aim of this study is to evaluate the regenerative potential of 3D biodegradable chitosan-PCL nerve conduit combined with BDNF-enriched secretome in peripheral nerve defects. In this study, biodegradable three-dimensional (3D) nerve conduits composed of polycaprolactone (PCL) and chitosan (75:25 wt/wt) were fabricated and used to bridge 10 mm sciatic nerve defects in rats. The conduits were evaluated alone or in combination with the secretome derived from Wharton's Jelly mesenchymal stem cells (WJ-MSC), either in the native form or enriched with brain-derived neurotrophic factor (BDNF). Thirty-two adult male Wistar Albino rats (mean weight 300-400 g) were randomized into four groups: Autograft (Group 1), conduit only (Group 2), conduit and WJ-MSC derived secretome (Group 3), and conduit combined with BDNF-enriched WJ-MSC derived secretome (Group 4). Functional recovery was assessed using the sciatic functional index (SFI), electromyography (EMG), and gastrocnemius muscle wet weight. Morphological and histological evaluations were performed at 12 weeks postoperatively. At the end of 12 weeks, Group 4 (-49.48 ± 2.82) exhibited significantly improved SFI values compared to Group 2 (-66.62 ± 5.31) and Group 3 (-60.60 ± 5.34) (p < 0.05). Electromyographic analysis revealed higher compound muscle action potential amplitutes in Group 4 (19.72 ± 3.62 mV) than Group 2 and Group 3 (p < 0.05), with values compared to the autograft group. Gasrtrocnemius muscle wet weight ratios were also significantly higher in Group 4 (69.09% ± 9.88%) than in Groups 2 and 3. Histological analyses showed enhanced axonal regeneration, reduced inflammation, and better myelination in Group 4. Scanning electron microscopy confirmed the conduit structural integrity and stability over the 12-week period. The combination of a 3D biodegradable chitosan-PCL conduit with BDNF-enriched WJ-MSC-derived secretome significantly enhanced peripheral nerve regeneration in a rat model. This strategy shows strong potential as an alternative to autografts for treating critical-sized nerve defects. Show less
Setmelanotide is a recently approved medication for patients over two years of age with monogenic obesity that emerges from POMC, LEPR, PCSK1 mutations, or Bardet-Biedl syndrome. While primarily targe Show more
Setmelanotide is a recently approved medication for patients over two years of age with monogenic obesity that emerges from POMC, LEPR, PCSK1 mutations, or Bardet-Biedl syndrome. While primarily targeting melanocortin-4 receptors (MC4R), setmelanotide also weakly stimulates melanocortin-1 receptors (MC1R), which may affect pigmentation. Clinical outcomes of this treatment modality remain limited due to the rarity of disorders mentioned above. We present a 12-year-old boy with a homozygous LEPR mutation who experienced skin hyperpigmentation shortly after the initiation of setmelanotide treatment. By the third month of treatment, gradual darkening of nevi was noted. At six-month follow-up, two nevi were excised due to pigmentation changes, and histopathology revealed dysplastic features in both. This case raises concerns about potential MC1R-mediated melanocytic activity during setmelanotide treatment. Therapy was temporarily discontinued. To our knowledge, this is the first reported pediatric case with LEPR-related monogenic obesity developing dysplastic nevi during setmelanotide use. Show less
Obesity and obesity-related breast cancer are major health problems that require alternative treatment strategies. Urtica dioica L. (U. dioica) stands out as a potential therapeutic candidate with its Show more
Obesity and obesity-related breast cancer are major health problems that require alternative treatment strategies. Urtica dioica L. (U. dioica) stands out as a potential therapeutic candidate with its anti-oxidant, anti-cancer and lipid-lowering properties. In this study, the molecular effects of U. dioica were investigated by gene expression analysis and molecular docking methods. U. dioica significantly suppressed the expression of Brca1, Brca2, Fas, Lpl, Dgat1 and Mcp1 genes, resulting in significant changes in lipid metabolism, cancer susceptibility and inflammation. Molecular docking analyses showed that U. dioica components have strong binding affinities with target proteins. In particular, the interactions between Dgat1-Isorhamnetin rutinoside (-10.3 kcal/mol), Fas-Quercetin acetyl rutinoside (-10.3 kcal/mol), Lpl-Apigenin hexoside (-9.2 kcal/mol) and Mcp1-Quercetin acetyl rutinoside (-8.6 kcal/mol) were notable. In vitro and in silico analyses supported each other, revealing the effects of U. dioica in gene expression regulation and the potential for its constituents to interact with proteins. These findings indicate that U. dioica may be a promising alternative therapeutic agent in the treatment of obesity and obesity-related breast cancer and emphasize that its efficacy should be confirmed by clinical trials. Show less
In recent years, there has been an increasing interest in producing new materials that use renewable resources and halogen-free flame retardants with nonleaching properties. This research focuses on d Show more
In recent years, there has been an increasing interest in producing new materials that use renewable resources and halogen-free flame retardants with nonleaching properties. This research focuses on designing and synthesizing phosphorus-nitrogen-based biopolyols for use in polyurethane (PU) foam production. Polyol (ESBO-DYM) with dual functionalities, renewability, and nonflammability is synthesized through the epoxy ring-opening reaction of epoxidized soybean oil with phosphorus and nitrogen-containing tetraol products (DYM). The mechanical and flame retardant properties of PU foams with the addition of an ESBO-DYM were investigated. Increasing the amount of phosphorus in the PU foams increased the thermal stability properties. Using 100% ESBO-DYM as a polyol in the foam formulation increased the limiting oxygen index (LOI) value to 22.9% and resulted in the highest char yield according to the thermal gravimetric analysis (17% at 600 °C). Additionally, the introduction of ESBO-DYM polyol into the formulation resulted in a decrease in the compression strength of the foams. The foam density decreased as the amount of ESBO-DYM polyol in the formulation increased. The foam with the highest amount of ESBO-DYM had a foam density of 29.1 kg/m Show less
Vitiligo is a chronic skin disorder in which immune dysregulation has been reported as one of the major etiopathological factors. Interleukin-12 (IL-12), IL-23 and IL-27 of IL-12 cytokine family were Show more
Vitiligo is a chronic skin disorder in which immune dysregulation has been reported as one of the major etiopathological factors. Interleukin-12 (IL-12), IL-23 and IL-27 of IL-12 cytokine family were identified as critical cytokines in the pathogenesis of many autoimmune and inflammatory skin diseases including vitiligo. IL-35 is one of the newest member of IL-12 cytokine family. The purpose of our study was to examine serum IL-35 levels in addition to serum IL-12, IL-23, IL-27 levels in the vitiligo patients and control group, and to investigate the relationship of these cytokines with the characteristics of vitiligo. Serum IL-12, IL-23, IL-27 and IL-35 levels of 87 vitiligo patients and 70 healthy volunteers were analyzed using the enzyme-linked immunosorbent assay (ELISA). We compared the IL-12 cytokine family levels in the patient and control groups, and investigated the relationship of these levels with the characteristics of vitiligo. Patients had higher levels of IL-12 (31.2 versus 20.1, P < 0.001) and IL-35 (9.6 versus 8.1, P = 0.031). Patient and control groups had similar levels of IL-23 (P = 0.78) but were correlated with the Vitiligo Area Scoring Index (VASI) (P = 0.022, r = 0.35). Patients had lower levels of IL-27 (207.6 versus 258.7, P < 0.001). In addition, the levels of serum IL-27 were correlated negatively with the Vitiligo Disease Activity (VIDA), and positively with disease duration (P = 0.007, r = 0.30). Differences of serum levels between Vitiligo patients and healthy controls, significant relationships with the characteristics of vitiligo suggest that the IL-12 cytokine family may play a role in the pathogenesis of vitiligo. Show less
Non syndromic monogenic obesity is a rare cause of early onset severe obesity in the childhood period. This form may not be distinguishable from other forms of severe obesity without genetic analysis, Show more
Non syndromic monogenic obesity is a rare cause of early onset severe obesity in the childhood period. This form may not be distinguishable from other forms of severe obesity without genetic analysis, particularly if patients do not exibit any physical abnormalities or developmental delay. The aim of this study was to screen 41 different obesity-related genes in children with non-syndromic early onset severe obesity. Children with severe (body mass index-standard deviation score >3) and early onset (<7 years) obesity were screened by next-generation sequencing based, targeted DNA custom panel for 41 known-obesity-related genes and the results were confirmed by Sanger technique. Six novel variants were identified in five candidate genes in seven out of 105 children with severe obesity; two in We identified six novel and four previously described variants in six obesity-related genes in 11 out of 105 childrens with early onset severe obesity. The prevalence of monogenic obesity was 10.4% in our cohort. Show less