The Notch pathway ligand Delta-like 4 (Dll4) functions as an antiangiogenic factor, inhibiting vascular endothelial growth factor (VEGF)-induced angiogenesis. This function is documented in tumor and embryonic vasculature. However, its implication in burn wounds remains unexplored. Our objective was to explore the involvement of the Notch in the healing of zone of stasis burns. We hypothesized that anti-Dll4 therapy would prevent progressive necrosis in the stasis zone by promoting angiogenesis. Burns were created in 21 rats using the comb burn model. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in the treatment group. Controls were given the same amount of solvent. Seven days after the burn, skin samples were evaluated for VEGF and Dll4 gene expressions. Immunohistochemical analysis was used for the assessment of vascular density, endothelial Dll4 expression, and apoptosis count. Histologic grading of tissue damage was performed. Circulating levels of VEGF and Dll4 were determined. VEGF and Dll4 mRNA levels were found to be simultaneously induced after the burn. In the treatment group, a significant increase in the number of vessels was observed. However, gross evaluation documented an expansion of necrosis to the zone of stasis with marked activation of apoptosis. Histologic assessment showed that the resultant vascular overgrowth was accompanied by extensive edema and abundant infiltration of leukocytes. We provide evidence for the involvement of Notch in the regulation of angiogenesis in zone of stasis burns.
1153Ehrlich Asit Solid Tümör Modeli Oluşturulmuş Farelerde Thymus sipyleus ve Taurinin Karaciğer MDA, GSH, AOPP Düzeylerine ve SOD Aktivitesine Etkileri Ö ÖZ ZE ET T A Am ma aç ç: : Bu ça lış ma da ta u rin (200 mg/kg/gün) ve Thymus sipy le us Bo iss. subs pe ci es sipy le us va ri ety sipy le us (ke kik) me ta nol özü tü (1.5 g/kg/gün) uy gu la ma sı nın Swiss al bi no fa re le rin ka ra ciğer do ku sun da ile ri dü zey ok si das yon pro te in ürün le ri (AOPP), ma lon di al de hit (MDA), glu tat yon (GSH) dü zey le ri ve sü pe rok sit dis mu taz (SOD) ak ti vi te si üze rin de ki et ki le ri araş tı rıl dı. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : De nek ler sağ lık lı kon trol, tü mör kon trol, ke kik ko ru ma, ke kik te da vi, ta u rin ko ru ma ve ta u rin te da vi ol mak üze re al tı gru ba ay rıl dı (n= 6). Ko ru ma grup la rı na tü mör en jek si yo nun dan sonra ki ilk gün den baş la ya rak 17 gün sü rey le mad de ve ril di. Te da vi grup la rı na tü mör en jek si yo nundan son ra 11. gün den iti ba ren yedi gün sü rey le mad de ve ril di. B Bu ul l g gu u l la ar r: : Tü mör kon trol ve ta u rin te da vi grup la rı kar şı laş tı rıl dı ğın da ta u rin te da vi gru bu nun AOPP dü ze yi nin an lam lı ola rak azal dı -ğı be lir len di (p< 0.05). Tü mör kon trol ve sağ lık lı kon trol grup la rı kar şı laş tı rıl dı ğın da tü mör kon trol gru bu nun AOPP dü ze yi nin art tı ğı göz len di; fa kat bu ar tış an lam lı bu lun ma dı (p> 0.05). Tü mör kontrol ve ta u rin ko ru ma grup la rı kar şı laş tı rıl dı ğın da ta u rin ko ru ma gru bu nun MDA dü ze yi nin anlam lı ola rak azal dı ğı be lir len di (p< 0.05). Tü mör kon trol ve ta u rin ko ru ma grup la rı kar şı laş tı rıl dı ğın da ta u rin ko ru ma gru bu nun GSH dü zey le ri nin art tı ğı göz len di; fa kat bu ar tış anlam lı bu lun ma dı (p> 0.05). Tü mör kon trol ve ke kik te da vi grup la rı kar şı laş tı rıl dı ğın da ke kik te davi gru bu nun SOD ak ti vi te si nin an lam lı ola rak art tı ğı be lir len di (p< 0.05). S So o n nu uç ç: : So nuç ola rak ta u rin uy gu la ma sı ok si da tif stres te ar tan MDA ve AOPP dü zey le ri ni azal tır ken GSH dü zey le ri ni ve SOD ak ti vi te si ni an lam lı ola rak et ki le me di. Thymus sipy le us me ta nol özü tü ise SOD ak ti vi te si ni ar tı rır -ken MDA, AOPP ve GSH dü zey le ri ni an lam lı ola rak et ki le me di.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Kar si nom, ehr lich tü mö rü; ta u rin; ok si da tif stres; ke kik A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : In this study, ef fects of ta u ri ne (200 mg/kg/day) and Thymus sipy le us Boiss. subs pe ci es sipy le us va ri ety sipy le us (thyme) met ha nol ex tract (1.5 g/kg/day) ad mi nis tra ti on on ad van ced oxi da ti on pro te in pro ducts (AOPPs), ma lon di al dehy de (MDA), glu tat hi o ne (GSH) le vels and su pe ro xi de dis mu ta se (SOD) ac ti vity in li ver tis su e of Swiss al bi no mi ce we re in ves ti ga ted. M Ma a--t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Test sub jects...
Notch inhibition significantly improved TRAM flap survival in animals exposed to nicotine by promoting VEGF-induced angiogenesis.
Öz Giriş ve Amaç: 19. kromozom (19q13.3-4) üzerinde bulunan 15 genden oluşan kallikrein ilişkili peptidazlar (KLK'lar), serin proteazların bir alt grubudur. Daha önce yapılan bazı çalışmalar KLK'ların çeşitli kanser türleriyle ilişkili olduğunu göstermiştir. Bununla birlikte, intrakranial tümörlerde KLK'ların tanı ve prognozdaki rolünü araştıran az sayıda çalışma bulunmaktadır. Bu nedenle, bu çalışmada intrakranial tümörlerde KLK5, KLK6 ve KLK7'nin ekspresyon düzeylerindeki değişimlerin belirlenmesi amaçlamıştır. Gereç ve Yöntemler: Menenjiom grade I (n = 15) ve glioblastoma multiforme (n = 15) tümör örneklerinde, KLK5, KLK6 ve KLK7 mRNA ekspresyon düzeyleri ters transkriptaz polimeraz zincir reaksiyonu (RT-PCR) kullanılarak tespit edildi. Protein ekspresyonları ise western blotting yöntemi kullanılarak belirlendi. Bulgular: KLK5 ve KLK7'nin mRNA ve proteinleri menenjiom grubunda daha sıklıkla ifade edilirken, KLK6'nın mRNA ve proteini glioblastoma grubunda daha sıklıkla ifade edilmektedir. Sonuç: Menenjiom ve glioblastoma grupları karşılaştırıldığında KLK5, KLK6 ve KLK7 mRNA ve protein ekspresyon düzeylerinde farklılıklar olduğu tespit edilmiştir. Bu genler intrakranial tümörlerin tanısı için yeni bir biyobelirteç olma potansiyeline sahip olabilir. Anahtar kelimeler: Kallikrein ilişkili peptidaz 5, kallikrein ilişkili peptidaz 6, kallikrein ilişkili peptidaz 7, menenjiom, glioblastoma
Purpose: In the study, it was aimed to determine the correlation between erythroferrone (ERFE) and hepcidin levels in patients with iron deficiency anemia and laboratory parametersused in diagnosing iron deficiency anemia, and to investigate whether the drugs that may lead to an increase in EFTE or will suppress hepcidin could be new treatmentmodalities in iron deficiency anemia. Method: 26 cases who presented to the pediatrics clinic with a diagnosis of iron deficiency anemia and did not have a concomitant disease and 26 healthy children were included in the study. In the study conducted with a case-control design, normal hemoglobin and hematocrit lower limits according to age and gender and red cell indices based on normal age and gender determined by the World Health Organization were used for the diagnosis of anemia. In order to evaluate iron status, serum iron, total iron binding capacity (TIBC), and ferritin levels were analyzed. Serum hepcidin and erythroferrone levels in children diagnosed with iron deficiency before the start of the iron treatment and at the end of first month of their treatment and in the control group were measured with ELISA method. Findings: Compared to the control group, hemoglobin (p < 0,001), MCV (p = 0,001), MCH (p < 0,001), MCHC (p < 0,001), iron (p < 0,001), ferritin (p < 0.001) and hepcidin (p = 0.001) levels in Group I were found to be significantly lower. Besides, RDW value was significantly higher in the iron deficiency group compared to the control group (p=0.001). When Group I and Group II values were compared, significant increases were determined in erythrocyte count (p=0.034), hemoglobin, hematocrit, MCV (p<0.001 for each), MCHC (p=0.002), iron (p<0.001), ferritin (p=0.015) and hepcidin levels (p<0.001). A significant decrease was found in iron binding capacity after the treatment (p=0.004). In Group I, hepcidin levels had a significant and strong correlation with initial ferritin levels (r = 0.829, p < 0.001). When erythrocyte levels of Group I and Group II were compared, there was a decrease in the erythrocyte levels of Group II, but this decrease was not statistically significant. However, hepcidin levels displayed moderate or weak correlation with neutrophil count (r = -0.429, p = 0.037), eosinophil count (r = -0.447, p = 0.029) and iron level (r = 0.594, p = 0.002). Conclusion: In the study, a strong and positive correlation was determined between ferritin and hepcidin levels in individuals with iron deficiency. This may suggest that hepcidin is largely regulated by iron deposit level. In addition, following the iron treatment, an increase was found in ferritin and hepcidin levels. In the study, no significant difference was found between theiron deficiency group and the control group in terms of erythroferrone levels.
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