Adana'daki ev dışı (outdoor) fungusların izolasyonu, identifikasyonu, mevsimsel dağılımı ve alerjik hastalıklarla ilişkilendirilmesi

TEZ6150Tez (Yüksek Lisans) -- Çukurova Üniversitesi, Adana, 2006.Kaynakça (s.67-76) var.viii, 77 s. : rnk. ; 29 cm.In this study, It was tried to determine the isolation, identification, seasonal distribution and correlation of allergic disases of outdoor fungi in ADANA, at 6 different area. For isolation of atmospheric fungi, samples collected from air with ECO MASS 100 Aerosampler equipment and plated on to the Rose Bengal Streptomycine Agar, then all plates incubated at 25.C for 14 days. Genus of the isolated fungus were identified based on micro- and macromorphology with the pigmentation of colonies at the bottom and surface of grown on CZ, MEA ad PDA media. Sampling was performed once a month, twelve times during the year, from february 2005 to January 2006. Total 3220 fungi colonies were isolated and as a result total 9 different genus of fungi were identified. These are Cladosporium 1436 (44,5%), Penicillium 644 (20%), Aspergillus 548 (17.0%), Alternaria 176 (5.4%), steril 63 (1.95%), Rhizopus 44 (1.36%), Fusarium 29 (0.90%), Acremonium18 (0.55%) Trichoderma 9 (0.27%), Chatemonium 1 (0.03%) and the others 252 (%7.8). A significant correlation was found between atmospheric fungi concentration and allergic diseases, the pediatric allergy clinic of Çukurova University Hospital,Bu çalışmada, Adana ilindeki 6 farklı istasyondan ev dışı (outdoor) mantarların izolasyonu, identifikasyonu, mevsimsel dağılımı ve alerjik hastalıklarla ilişkisi saptanmaya çalışılmıştır. Atmosferik Fungusların izolasyonu amacıyla örnekler, ECO MASS 100 Mikrobiyal Hava İzleme Sistemi kullanılarak Rose Bengal Streptomycine Agarlı Besiyerlerine ekim yapılmıştır. PDA, MEA, CZ besiyerlerindeki üreme davranışları, koloni morfolojisi, pigment oluşumu, petri kutusunda alt ve üstten görünüşleri, spor ve hifsel yapılarının mikroskobik incelenmesi gibi parametrelere göre tanımlama kriterleri dikkate alınarak identifikasyonları genus düzeyinde gerçekleştirilmiştir. Örnekleme Şubat 2005-Ocak 2006 tarihleri arasında ayda bir kez olmak koşuluyla 12 kez yapılmıştır. Toplam 3220 mantar kolonisi izole edilmiştir. İzole edilen kolonilerin tanımlanması sonucu 9 farklı mantar cinsi saptanmıştır. Bunlar; Cladosporium 1436 (%44,5), Penicillium 644 (%20), Aspergillus 548 (%17.0), Alternaria 176 (%5.4), steril 63 (%1.95), Rhizopus 44 (%1.36), Fusarium 29 (%0.90), Acremonium18 (%0.55) Trichoderma 9 (%0.27, Chatemonium 1 (%0.03) ve diğerleridir 252 (%7.8) Atmosferdeki mantar konsantrasyonu ile alerjik çocukların astım skorları ve rinit skorları arasında ileri düzeyde anlamlı ilişki saptanmıştır.Bu çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi Tarafından Desteklenmiştir. Proje No:FEF2005YL

Kinome-wide RNAi screening for mediators of ABT-199 resistance in breast cancer cells identifies Wee1 as a novel therapeutic target

Antiapoptotic and proapoptotic BCL-2 protein family members regulate mitochondrial apoptotic pathway. Small molecule inhibitors of antiapoptotic BCL-2 proteins including BCL-2-specific inhibitor ABT-199 (Venetoclax) are in clinical development. However, the efficiency of ABT-199 as a single agent in solid tumors is limited. We performed a high-throughput RNAi kinome screen targeting 691 kinases to identify potentially targetable kinases to enhance ABT-199 response in breast cancer cells. Our studies identified Wee1 as the primary target kinase to overcome resistance to ABT-199. Depletion of Wee1 by siRNA-mediated knockdown or inhibition of Wee1 by the small molecule Wee1 inhibitor AZD1775 sensitized SKBR3, MDA-MB-468, T47D and CAMA-1 breast cancer cells to ABT-199 along with decreased MCL1. BH3-only proteins PUMA and BIM functionally contribute to apoptosis signaling following co-targeting BCL-2 and Wee1. Suppression of Wee1 function increased mitochondrial cell death priming. Furthermore, we found that Wee1 inhibition altered MCL1 phosphorylation and protein stability, which led to HUWE1-mediated MCL1 degradation. Our findings suggest that Wee1 inhibition can overcome resistance to ABT-199 and provide a rationale for further translational investigation of BCL-2 inhibitor/Wee1 inhibitor combination in breast cancer

Mitochondrial estrogen receptors alter mitochondrial priming and response to endocrine therapy in breast cancer cells

Breast cancer is the most common cancer with a high rate of mortality and morbidity among women worldwide. Estrogen receptor status is an important prognostic factor and endocrine therapy is the choice of first-line treatment in ER-positive breast cancer. However, most tumors develop resistance to endocrine therapy. Here we demonstrate that BH3 profiling technology, in particular, dynamic BH3 profiling can predict the response to endocrine therapy agents as well as the development of acquired resistance in breast cancer cells independent of estrogen receptor status. Immunofluorescence analysis and subcellular fractionation experiments revealed distinct ER-alpha and ER-beta subcellular localization patterns in breast cancer cells, including mitochondrial localization of both receptor subtypes. shRNA-mediated depletion of ER-beta in breast cancer cells led to resistance to endocrine therapy agents and selective reconstitution of ER-beta in mitochondria restored sensitivity. Notably, mitochondria-targeted ER-alpha did not restore sensitivity, even conferred further resistance to endocrine therapy agents. In addition, expressing mitochondria-targeted ER-beta in breast cancer cells resulted in decreased mitochondrial respiration alongside increased total ROS and mitochondrial superoxide production. Furthermore, our data demonstrated that mitochondrial ER-beta can be successfully targeted by the selective ER-beta agonist Erteberel. Thus, our findings provide novel findings on mitochondrial estrogen signaling in breast cancer cells and suggest the implementation of the dynamic BH3 technique as a tool to predict acquired endocrine therapy resistance

Mitochondrial estrogen receptors alter mitochondrial priming and response to endocrine therapy in breast cancer cells

Breast cancer is the most common cancer with a high rate of mortality and morbidity among women worldwide. Estrogen receptor status is an important prognostic factor and endocrine therapy is the choice of first-line treatment in ER-positive breast cancer. However, most tumors develop resistance to endocrine therapy. Here we demonstrate that BH3 profiling technology, in particular, dynamic BH3 profiling can predict the response to endocrine therapy agents as well as the development of acquired resistance in breast cancer cells independent of estrogen receptor status. Immunofluorescence analysis and subcellular fractionation experiments revealed distinct ER-alpha and ER-beta subcellular localization patterns in breast cancer cells, including mitochondrial localization of both receptor subtypes. shRNA-mediated depletion of ER-beta in breast cancer cells led to resistance to endocrine therapy agents and selective reconstitution of ER-beta in mitochondria restored sensitivity. Notably, mitochondria-targeted ER-alpha did not restore sensitivity, even conferred further resistance to endocrine therapy agents. In addition, expressing mitochondria-targeted ER-beta in breast cancer cells resulted in decreased mitochondrial respiration alongside increased total ROS and mitochondrial superoxide production. Furthermore, our data demonstrated that mitochondrial ER-beta can be successfully targeted by the selective ER-beta agonist Erteberel. Thus, our findings provide novel findings on mitochondrial estrogen signaling in breast cancer cells and suggest the implementation of the dynamic BH3 technique as a tool to predict acquired endocrine therapy resistance.Science Academy BAGEP progra

CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers

Cytochrome P450 (CYP450) is a major enzyme system involved in drug metabolism as well as regulation of brain function. Although individual variability in CYP enzymes have been studied in terms of personality traits and treatment effects, no study up to now evaluated CYP polymorphisms in children with attention deficit/hyperactivity disorder (ADHD). We aimed to define the genetic profiles of CYP2D6 and CYP2C19 relevant alleles in children with ADHD according to treatment status and compare the frequencies according to past results. Three hundred and seventeen patients with ADHD-Combined Presentation were enrolled; symptom severity was evaluated by parents and clinicians while adverse effects of previous treatments were evaluated with parent and child reports. Reverse blotting on strip assays was used for genotyping and descriptive and bivariate analyses were conducted. A p-value was set at 0.05 (two-tailed). Children were divided into treatment-naïve (n=194, 61.2%) and treatment-resistant (n=123, 38.8%) groups. Within the whole sample PM, EM and UM status according to 2D6 were 3.8% (n=12), 94.3% (n=299) and 21.9% (n=6); respectively. PM, IM, EM and UM status according to 2C19 were 2.5% (n=8), 19.8% (n=63), 48.6% (n=154) and 29.0% (n=92), respectively. No relationship with treatment resistance, comorbidity or gender could be found. Importantly, CYP2C19 UMs were significantly more frequent in ADHD patients compared to previous studies in the general population. CYPs may be a rewarding avenue of research to elucidate the etiology and treatment of patients with ADHD

RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells

Ovarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial outer membrane permeabilization by either increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. In particular, BAX expression negatively correlates with RAB25 expression in ovarian cancer cells. BH3 profiling assays corroborated that RAB25 decreases mitochondrial cell death priming. Suppressing RAB25 by means of RNAi or RFP14 inhibitory hydrocarbon-stapled peptide sensitizes ovarian cancer cells to chemotherapy as well as RAB25-mediated proliferation, invasion and migration. Our data suggest that RAB25 is a potential therapeutic target for ovarian cancer

Cytokine expression profiles in Autism spectrum disorder: A multi-center study from Turkey

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction as well as restricted interests and repetitive behaviors. The pathogenesis of ASD is not completely understood, but a growing body of research has demonstrated that the immune response may be a contributing factor in the etiology and/ or ontogeny of ASD. The aim of this study was to determine the expression levels of IL-1ß, IL-1?, IL-4, IL-6, IL-17, TNF-? and TGF-ß in peripheral blood mononuclear cells of children with ASD and healthy controls in order to determine the contributions of cytokines to ASD. Within the study timeframe, 195 children with ASDs (80.5% male) and 162 controls (73.6% male) were enrolled. Most children with ASD had a comorbid disorder (n = 114, 58.5%), with the most common diagnoses as Intellectual Developmental Disorder (IDD, n = 64, 32.8%) and ADHD (n = 64, 32.8%). The majority of children with ASD had severe autistic symptoms as evaluated via Childhood Autism Rating Scale (CARS, n = 130, 64.6%). The mean CARS score in the ASD sample was 40.8 (S.D. = 7.6). The patients with ASD were found to have significantly higher levels of IL-6 (p 0.001) and significantly lower levels of IL-17 (p 0.05, all Bonferroni corrected). Treatment tended to affect IL-4 levels. Lastly, discriminant function analysis (DFA) revealed that a combination of IL-6, IL-17 and IL-1? correctly classified 56.6% of cases. Despite extensive immunological evidence suggesting immune system aberrations, further research is required to clarify the relationship between immune profiles and ASD symptoms. © 2020 Elsevier Lt

Cytokine expression profiles in children and adolescents with tic disorders

Abstract The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette’s disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1β, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions

Cytokine expression profiles in children and adolescents with tic disorders

The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette's disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1 beta, TNF-alpha, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions