This study aimed to investigate the effects of ozone exposure on apoptotic mechanisms in primary (Colo-320) and metastatic (Colo-741) cell lines. Colo-320 and Colo-741 cells were grown in RPMI-1640 medium supplemented with 10

Abstract Approximately 70% of newly diagnosed breast cancer patients are estrogen receptor positive. Patients treated with approved treatment strategies may develop resistance to these therapies. Because of this problem in treatment, new treatment regimens need to emerge. Altered reprogramming of metabolism and an intense dependence on glycolysis are hallmarks of cancer, which is necessary to support the high energy demand of rapidly proliferating cancer cells. Rapidly dividing cancer cells are known to have increased energy requirements and altered reprogramming of glucose metabolism, leading to an increased reliance on glycolysis. The conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, a critical rate-limiting step in the glycolysis pathway, is greatly influenced by an allosteric activator produced by the enzyme PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), thus making PFKFB3 an important regulator of glycolytic flux. Furthermore, PFKFB3 has been shown to be overexpressed in many human cancers, including breast cancer, and upregulated by estrogen. In our previous studies, we have shown that endocrine-resistant BC cells growth is strongly reduced by PFKFB3 targeting using PFKFB3 inhibitors, glucose uptake is reduced, triggered to necroptosis by RIPK1 and MLKL phosphorylation, and PFKFB3 inhibition reduces tumor size in mouse xenografts. In this study, we showed that silencing of RIPK1 and MLKL, genes involved in necroptosis, by siRNAs followed by inhibition of PFKFB3 by PFK158 did not induce necroptosis in endocrine-resistant BC cells. Furthermore, we further confirmed that phosphorylation of MLKL and RIPK occurs with PFKFB3 inhibition. In summary, this study reveals that necroptosis induced by PFKFB3 inhibition contributes to resistance by arresting necroptosis in endocrine-resistant BC cells after silencing of necroptosis-related genes. Citation Format: Brandon C. Jones, Tuna Onal, Surojeet Sengupta, Catherine M. Sevigny, Lu Jin, Paula R. Pohlmann, Ayesha Shajahan-Haq, Robert Clarke. Silencing of necroptosis related genes in endocrine-resistant breast cancer cells causes PFKFB3 induced arrest of necroptosis and contributes to resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3281.

Objective The aim of this study was to evaluate the effects of high molecular weight hyaluronic acid (HMWHA) and low molecular weight hyaluronic acid (LMWHA) on alveolar bone remodelling during orthodontic tooth movement (OTM).Materials and methods The study involved 60 Wistar-Albino rats, divided into two main groups and further divided based on time periods (1, 3, 7, 14, and 21 days) therefore containing 6 rats in each subgroup. Orthodontic mesialisation of the maxillary first molars was bilaterally achieved using nickel-titanium closed coil springs. In Group I, the right side was injected with HMWHA, while in Group II, the right side was injected with LMWHA. The left side of all rats was injected with normal saline. OTM was measured using 3-dimensional digital models. Alveolar bone volume in the interradicular areas of the first molars was evaluated through histomorphometric and immunohistochemical analyses of receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG).Results Histologically, on days 14 and 21, the number of osteoclasts on the experimental sides was higher than on the control sides in both groups. On day 21, the amount of OTM in the HMWHA-injected group was 1.4 times greater than in the control group. Both types of hyaluronic acid increased the RANKL/OPG ratio.Conclusion The injection of HA may accelerate orthodontic tooth movement by decreasing alveolar bone density and enhancing bone cell proliferation.

Abstract Disclosure: K.A. de Oliveira: None. F.D. Andrade: None. M. Ozgul-Onal: None. A. Yadav: None. T. Onal: None. L. Jin: None. S. Sengupta: None. R. Clarke: None. Endocrine therapy can lead to cellular nutrient deprivation by reducing glucose and glutamine uptake and total cellular ATP production in breast cancer cells. The ability to bypass this metabolic stress is fundamental to how breast cancer cells regulate growth and acquire endocrine resistance. SIRT3, which can be activated by calorie restriction, modulates mitochondrial adaptation to low energy input. It has a key role in mitochondrial integrity and function, regulating cell survival, death, and metabolism, regulating the shift to amino-acid and fatty-acid catabolism. SIRT3 can maintain ROS levels at the appropriate levels for sustaining a proliferative phenotype, preventing apoptosis and promoting carcinogenesis. A role of SIRT3 in epigenetic regulation has also been reported. The ability of SIRTs to sense and respond to changes in energy, coupled with their intrinsic deacetylase/deacylase functions, could provide a mechanism for the cell to rewire signaling and maintain a newly acquired drug-resistant phenotype. Using antiestrogen sensitive (LCC1) and cross-resistant (LCC9) breast cancer cells, we confirmed higher expression of SIRT3 in LCC9, compared with LCC1 cells. Upregulation of SIRT3 expression within 24 hrs of Fulvestrant (ICI 1 µM) treatment (p=0.0176) in LCC1 was shown, whereas no effect was observed in LCC9 cells. Inhibition of SIRT3 activity, using the inhibitor LC0296 (15 µM), reduced growth rate in both LCC1 and SIRT3-silenced LCC9 cells under treatment with ICI (p<0.0001, p<0.001 respectively). Treatment with SIRTUIN 3 inhibitor and ICI induced caspase-independent cell death in LCC1 and SIRT3-silenced LCC9 cells compared to the untreated control and ICI only treated cells (p<0.001). The combination of SIRT3 inhibition (LC0296, 15 µM) and ICI treatment (0.5 µM) increased ROS production in LCC9-SIRT3 silenced cells in 24 hrs compared with the untreated control and ICI only treated cells (p<0.001). The combination of LC0296 and ICI induced a decrease in mitochondrial membrane potential and ATP production, and a decrease in glycolytic capacity and glycolytic reserve in both LCC1 and SIRT3-silenced LCC9 cells, compared with the untreated control (p<0.001). Moreover, ICI significantly reduced ATP production in the mitochondria of the SIRT3-silenced LCC9 cells (p<0.001) but not in the non-silenced (control) LCC9 cells. Taken together, these results show that SIRT3 may have a key role in determining the response to fulvestrant response in ER+ breast cancer cells; a more detailed understanding of this role for SIRT3 is under investigation in our laboratory. Presentation: Thursday, June 15, 2023

BACKGROUND:The gut microbiota modulates nervous system function. In the literature, it has been shown that this modula-tion is used in many nervous system injuries through oxidative stress (OS) and apoptosis mechanisms. In this study, it was aimed to investigate the neuroprotective effects of probiotic (PB) treatment in a rat traumatic brain injury (TBI) model with histological and electroencephalographic (EEG) data.METHODS:Forty male Wistar albino rats were divided into four groups. Group 1 was the control group (CONTROL, n=10) and no trauma was applied. Group 2 was the trauma group with the weight-drop technique (TBH, n=10). Group 3 was the sham group (SHAM), (TBH+sterile saline [SS], n=10) rats were given 500 µL of SS per day by oral gavage. Group 4 was the PB treatment group, (TBH+PB, n=10) rats were treated daily for 7 days with 500 µL of PB oral gavage. Brain samples were collected 7 days after trauma. Histopathological evaluation of brain samples was done with HE. OS with Endothelial nitric oxide synthase, vascularization with Vas-cular Endothelial Growth Factor, gliosis with S100, and apoptosis with caspase 3 were evaluated immunohistochemically. Apoptotic index was determined with TUNEL. In addition, EEG and somatosensory evoked potential (SEP) recording findings were compared.RESULTS:It was determined by HE staining that there was a significant (P<0.001) damage in the TBI and sham groups compared to the control group. It was found that PB treatment provided a significant (P<0.01) improvement in the damage created. While OS (P<0.01), gliosis (P<0.01), and apoptosis (P<0.05) decreased with PB treatment, angiogenesis (P<0.01) increased. In support of these findings, in the software-mediated EEG and SUP examination; Delta wave power and theta/alpha ratio increased with TBI and de-creased with PB treatment.CONCLUSION:The results showed that PB treatment provided a significant improvement in rats by reducing OS, apoptosis, and gliosis and increasing vascularity. To the best of our knowledge in the literature, it was shown for the 1st time that histological results for the treatment of PB were supported by software-mediated EEG and SEP analysis.

Aim The dorsal nerve of the penis (DNP) is the terminal branch of the pudendal nerve which is responsible for the somatic innervation of the penis. This study aims to outline any direct role of the DNP in the hemodynamics of erection histologically and physiologically. Materials and Methods Fifteen Wistar albino rats were sorted into the electrical activity (n = 6), intracavernous pressure (n = 4), and control (n = 5) groups. The dorsal nerve was electrostimulated and the simultaneous changes in intracavernous pressure and smooth muscle activity were recorded. Penile tissues were collected, fixed, and sectioned, the slides were stained with either hematoxylin-eosin for morphological evaluation or using the indirect immunoperoxidase technique to analyze the distributions of eNOS, iNOS, and nNOS. Results During electrostimulation, there was a simultaneous statistically significant decrease in the electrical activity inside the corpora in electromyography and an increase in intracavernous pressure. eNOS and iNOS immunoreactivities were higher in the study group than in the control group. nNOS immunoreactivity was moderate in both study and control groups. Conclusion Some fibers in the dorsal nerve of penis continue into the corpora cavernosa through the tunica albuginea and have an active, direct role in the hemodynamic process of erection, which may be complementary to the main route of innervation.

Актуальність. Рецептори гіалуронану відіграють певну роль при різних типах раку. Однак зміни, що відбуваються в рецепторах CD44 та RHAMM після введення рапаміцину, потребують пояснення. Мета дослідження: вивчити зміни рецепторів гіалуронової кислоти CD44 і RHAMM після введення рапаміцину в клітинних лініях MCF-7 та MDA-MB-231. Матеріали та методи. Клітинні лінії MCF-7 і MDA-MB-231 культивували в стандартних умовах та забарвлювали з використанням первинних антитіл до CD44 і RHAMM для виявлення білків. Значення H-score визначали за інтенсивністю імунореактивності. Рівень експресії CD44 і RHAMM оцінювали за допомогою методу полімеразної ланцюгової реакції в реальному часі (qRT-ПЛР). Результати. У клітинних лініях MCF-7 і MDA-MB-231 імунореактивність CD44 та RHAMM знизилася на 24-ту годину після введення рапаміцину порівняно з контрольною групою. Відповідно до результатів використання qRT-ПЛР, експресія CD44 (p <0,033) та RHAMM (p<0,0002) зменшилася в групі, що отримувала рапаміцин, порівняно з контрольною групою. Висновки. Рапаміцин знижував вплив рецепторів гіалуронану на клітинні лінії раку молочної залози. Таким чином, знову наголошено на важливості позаклітинного матриксу при раку молочної залози.

Mixed lineage kinase domain-like pseudokinase (MLKL) is the terminal and indispensable mediator of necroptosis. Necroptosis, also known as programmed cell necrosis, is a caspase-independent cell death mechanism involved in various pathologic and inflammatory processes. Triggering necroptosis could be an alternative approach in treating apoptosis-resistant cancer cells to prevent recurrent disease. In addition to its function in necroptosis, MLKL plays a role as a regulator in many cellular processes independent of necroptosis. A better understanding of the intracellular function of MLKL and its role in various diseases and pathologic conditions is needed to enable discovery of new targeted therapies. Various necroptosis-dependent and independent functions of MLKL are reviewed in this chapter, with a focus on functions of MLKL in necroptosis, autophagy, inflammation, tissue regeneration, and endosomal trafficking.

Amaç: Barsak mikrobiyatası ile beyin arasında iki yönlü bir ilişki olup özellikle travmatik beyin hasarı (TBH) sonrası hasarda oksidatif stres ve enflamatuvar aşama önemli bir role sahiptir.Barsakta oluşan patoloji bu hasarın tedavisinde problem oluşturmaktadır.Probiyotikler (PB) bunu düzenleyerek oluşan oksidatif stres ve gliozisi azaltabilme potansiyelindedir.Bu çalışmada sıçan modelinde TBH oluşturulup PB için bu olası etki

Polycystic ovary syndrome (PCOS) is a complex disorder in which the aetiology is still not explained very well. The PI3K/PTEN (phosphatidylinositol 3-kinase/phosphatase and tensin homolog deleted on chromosome 10) pathway is an important pathway that is involved in many mechanisms, including proliferation, growth and motility. PTEN plays a role in granulosa cell proliferation and regulates the differentiation process. The aim of this study was to investigate the expression levels of Pten and Pik3ca in PCOS mouse models with and without any treatment procedures. Three groups of mouse models, PCOS, a PCOS group with clomiphene citrate treatment, and a PCOS group with the combination of clomiphene citrate, metformin and pioglitazone treatment, were established. Ovarian tissues, which were obtained from these groups and a control group with no PCOS, were embedded in paraffin and RNA was extracted. cDNA was synthesized and real-time PCR was conducted to evaluate the expression levels of Pten and Pik3ca. The results of this study showed that both Pten and Pik3ca genes were expressed in the ovarian tissues from the mouse models. Although one-way analysis of variance results showed that Pten was expressed significantly differently in the samples, individual Student's t-tests did not show any significantly different expression levels in each group. This study is important as it shows the expression patterns of two genes in PCOS mouse models with different treatment strategies, including clomiphene citrate, metformin and pioglitazone. The results of this study formed the basis of research studies and investigations into different genes within the PTEN pathway, as well as other pathways that are under investigation.

AimIn this study, it was aimed to evaluate effects of dexmedetomidine (DEX) on the damage model induced by hypoxia-ischemia in oxygen and glucose deprivation (OGD) through cell viability (MTT), inflammation (iNOS, eNOS, IL-6, and TGF-b), apoptosis (TUNEL) in the neuroblastoma cell line of mouse origin (NB2a).Materials and MethodsThe effects of DEX on cell viability and toxicity were analyzed with MTT and NTT. Four groups were established for observing the effects of hypoxia-ischemia in the oxygen and glucose deprivation (OGD) model. Control group (C); Cells are incubated with DMEM high glucose medium for 4 hours in normoxic condition. OGY group: Cells are incubated in the oxygen and glucose deprivation (OGD) medium for 4 hours in hypoxic condition which have a gas mixture of 5% CO2, 1% O2 and 92% N2 for 4 hours in hypoxic chamber. DEX+OGD group: Before the OGD procedure, cells are treated with DEX 10 µM for 3 hours. OGD+DEX group: After the OGD procedure, cells were treated with DEX 10 µM for 3 hours. Inflammatory effects were tested by immunohistochemistry and H-scores belonging to antibodies of iNOS, eNOS, and TGF-b were calculated. Apoptotic effects of DEX were tested by the TUNEL method. Data were analyzed one-way ANOVA and Kruskal-Wallis. Data were given mean±SD. p<0.05 is statically significant.ResultsDexmedetomidine increased the cell viability in those all concentrations (0.1-45 µM) except 60 uM (p<0.01, Figure 1a). H-score value belongs to eNOS antibody decreased significantly with DEX 10 mm in DEX+OGD group and OGD+DEX group compared to OGD group (p<0.001, Figure 1b). H-score value belongs to IL-6 antibody did not show any difference between OGD, DEX+OGD, and OGD+DEX groups (Figure 1d). H-score value belongs to TGF-b antibody significantly decreased with DEX 10 mM in DEX+OGD group and OGD+DEX group compared to OGD group (p<0.0001, Figure 1d). The apoptotic index decreased significantly in the DEX+OGD group and OGD+DEX group compared to Group OGD (p<0.001, Figure 1f)ConclusionsDexmedetomidine increased the cell viability in those almost all concentrations (0.1-45 µM) except 60 µM. Either before or after injury treatment with DEX 10 mM decreased apoptosis induced by hypoxia-ischemia in NB2a cells. Treating with DEX 10 mM before OGD injury decreased both iNOS and eNOS antibodies as well. Neuroprotective effects of DEX against OGD injury might be due to antiapoptotic and antioxidative effects. In this study, it was aimed to evaluate effects of dexmedetomidine (DEX) on the damage model induced by hypoxia-ischemia in oxygen and glucose deprivation (OGD) through cell viability (MTT), inflammation (iNOS, eNOS, IL-6, and TGF-b), apoptosis (TUNEL) in the neuroblastoma cell line of mouse origin (NB2a). The effects of DEX on cell viability and toxicity were analyzed with MTT and NTT. Four groups were established for observing the effects of hypoxia-ischemia in the oxygen and glucose deprivation (OGD) model. Control group (C); Cells are incubated with DMEM high glucose medium for 4 hours in normoxic condition. OGY group: Cells are incubated in the oxygen and glucose deprivation (OGD) medium for 4 hours in hypoxic condition which have a gas mixture of 5% CO2, 1% O2 and 92% N2 for 4 hours in hypoxic chamber. DEX+OGD group: Before the OGD procedure, cells are treated with DEX 10 µM for 3 hours. OGD+DEX group: After the OGD procedure, cells were treated with DEX 10 µM for 3 hours. Inflammatory effects were tested by immunohistochemistry and H-scores belonging to antibodies of iNOS, eNOS, and TGF-b were calculated. Apoptotic effects of DEX were tested by the TUNEL method. Data were analyzed one-way ANOVA and Kruskal-Wallis. Data were given mean±SD. p<0.05 is statically significant. Dexmedetomidine increased the cell viability in those all concentrations (0.1-45 µM) except 60 uM (p<0.01, Figure 1a). H-score value belongs to eNOS antibody decreased significantly with DEX 10 mm in DEX+OGD group and OGD+DEX group compared to OGD group (p<0.001, Figure 1b). H-score value belongs to IL-6 antibody did not show any difference between OGD, DEX+OGD, and OGD+DEX groups (Figure 1d). H-score value belongs to TGF-b antibody significantly decreased with DEX 10 mM in DEX+OGD group and OGD+DEX group compared to OGD group (p<0.0001, Figure 1d). The apoptotic index decreased significantly in the DEX+OGD group and OGD+DEX group compared to Group OGD (p<0.001, Figure 1f) Dexmedetomidine increased the cell viability in those almost all concentrations (0.1-45 µM) except 60 µM. Either before or after injury treatment with DEX 10 mM decreased apoptosis induced by hypoxia-ischemia in NB2a cells. Treating with DEX 10 mM before OGD injury decreased both iNOS and eNOS antibodies as well. Neuroprotective effects of DEX against OGD injury might be due to antiapoptotic and antioxidative effects.

Abstract Aim Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disease and is the most common cause of infertility in women due to ovulation disorder. Although the distinctive morphological features of the polycystic ovary were clearly evaluated, the specific oocyte maturation molecules that are affect oocyte maturation and oocyte quality are currently not understood. In addition, the effect of drugs used to induce ovulation in PCOS on oocyte maturation is unknown. In this study it is aimed to investigate the changes of oocyte maturation proteins (Nobox, Foxl2, Cep55, Cx37, Cx43) post ovulation induction treatment. Materials and Methods Four-week-old, female Balb/c mice were subcutaneously injected 6mg/100g dehydroepiandrosterone (DHEA) for 21 consecutive days for experimental PCOS models and divided four groups. In control group, no injections performed. PCOS group, after DHEA administration was not applied any treatment. Treatment groups were given clomiphene citrate (1,5 mg/kg) alone or clomiphene citrate (1,5 mg/kg), metformin (12 mg/kg) and pioglitazone (0,20 mg/kg) as a combine for consecutive 5 days. The distributions of molecules were evaluated by indirect immunoperoxidase staining method in ovarian tissues and immunofluorescence staining method for oocytes. Intensity of immunofluorescence evaluated by ImageJ. Results The formation of the PCOS model was demonstrated by the glucose tolerance test, histological and morphological evidence. It was determined that the expression of all investigated molecules significantly decreased in the ovarian tissues of PCOS group but increased in the treated groups. In oocytes, intensities of Nobox, Foxl2, Cep55 and Cx43 were significantly increased in clomiphene citrate administered group compared to the PCOS group. Conclusion This study is the first to investigate the effect of drugs used for providing ovulation induction and reducing insulin resistance as single or combined treatments in PCOS mice model through maturation molecules. Both in vivo and in vitro oocyte maturation may trigger with target-specific treatment in PCOS patients. In addition, new molecules could be used in control of the in vitro oocyte maturation during treatment.

Giriş ve Amaç: Diyabetik deri yarası kronik, tedavisi zor ve maliyetli bir patolojidir Probiyotikler (PB) yeni ürünler olup barsak mikrobiyotasını düzenleyerek cilt yaralarının iyileşme sürecini olumlu yönde etkilerler. Ancak mekanizmaları bilinmemektedir. Bu çalışmada diyabetik sıçan deri yarasına PB katkısı morfolojik parametreler, oksidatif stres, apoptoz, damarlanma, inflamasyon ve bağ doku açısından mekanizmalar araştırıldı. Gereç ve Yöntemler: Sıçanlar 50 mg/kg intraperitoneal Streptozotosin kullanılarak diyabetik hale getirildi. Sırt bölgesinde 1x1cm tam kat deri defekti yapıldı ve NBL Probiotic Gold preparatı PB olarak oral gavaj ile uygulandı. Yara iyileşmesinin 7. gününde örnekler alındı. Histokimyasal olarak HE boyamaları ile morfolojik inceleme ve skorlama yapıldı. Örnekler, immünohistokimyasal yöntem ile eNOS, Kaspas 3, IL-10, VEGF ve Kollagen1 ile boyandı ve H-skor ile değerlendirildi. Bulgular: Tam kat deri defekti ile oluşan yaranın iyileşmesinde PB kullanımı morfometrik skorlamada anlamlı bir hızlanma ve olgunlaşma sağladı. Yara yerinde hasara bağlı oluşan eNOS, Kaspas 3 ve IL-10 artışı ile VEGF ve Kollagen1 azalışının PB ile anlamlı bir şekilde geri döndürüldüğü izlendi. Sonuç: PB için deride kronik, zor ve maliyetli yara iyileşmesi üzerindeki olumlu etkisinin klinikte hasta yaşam kalitesini arttıracağı düşünülmektedir.

Polycystic ovary syndrome (PCOS) is a complex disorder and genetic factors are believed to play a role. The main aim was to investigate expression levels of genes involved in PI3K/AKT signalling pathway pretreatment and post-treatment. Mouse models of PCOS were generated. Group one included control mice with no polycystic ovaries (n = 4), Group 2 included a PCOS mouse model (n = 8), Group 3 included PCOS mice treated with clomiphene citrate (n = 7) and Group 4 included PCOS mice treated with clomiphene citrate, metformin and pioglitazone (n = 8). Histochemical analyses were performed. Total RNA was extracted and cDNA was synthesized. Irs, Akt1 and Akt2, mTor and Pdpk1 gene expression levels were evaluated by RT-PCR amplification. In Group 1, cortex and medulla were evaluated as normal; in Group 2, ovarian cortex was composed of immature oocytes and cystic follicles with atretic follicles. In Groups 3 and 4, follicles were in the process of normal follicle differentiation. The expression levels of Akt1 and Pi3k were significantly different (P < 0.0001) between Groups 1 and 2. The significant differences in expression levels of Pi3k and Akt1 were also observed between the Group 1 and both Groups 3 and 4 (P < 0.0001). Furthermore, significant variations of the expression levels of mTor between Groups 1 and 4 were observed. The extrapolation of results of this study may imply that follicular development may be regulated by molecular pathways involving Pi3k, Akt1 and mTor expression. Therefore, genes in the PI3K/AKT pathway may have a direct regulatory role in the development of PCOS.

Docetaxel (DTX) is a widely used chemotherapeutic agent in breast, prostate and lung cancers. Approximetly 60% of patients face ocular disorders including epiphora, stye, blepharedema, dacryostenosis, corneal and conjunctival disorders, entropion and blurred vision. The aim of this study is to investigate the effects of DTX on rat eye This study mainly planned to assess the alopecia effect of DTX, but the remained eye tissues have been evaluated to decrease the animal number used in medical researches. 6-8 months old albino male Wistar rats ( n  = 7) were given 10 mg/kg intraperitoneally (i.p) DTX treatment three times at the 0th, 8th, 15th days. Control group ( n  = 6) was administered serum physiologic i.p once a week. The ocular tissues are taken at the 22nd day and evaluated by Hematoxylin&Eosin staining. TGF-beta and TNF-alfa stains were planned. Preliminary results of this study revealed conjunctival epithelial degeneration, corneal neovascularization, mild-severe retinal nerve fibre layer degeneration, inflammation and cystic dilatation of lacrimal gland, increased capillary vessel density and vacuolar degeneration of optic nerve. The findings were demonstrated in Fig 1,2 and 3. DTX cause serious ocular disorders and this is the first experimental study investigating these effects histologically. Increasing number of cancer cases and frequent use of Docetaxel, urges ophthalmologist to be aware of its ocular side effects.

Amaç: Probiyotik (PB) ve Mezenkimal Kök Hücre (MKH) yeni tedavi fikirleridir. PB ile değiştirilen mikrobiyata farklı etkiler yapmaktadır. Son zamanlarda önemli araştırma konusu olmuştur. MKH hücresel tedavi kapsamında MKH Graft Versus Host (GVH) gibi hastalıklarda klinik uygulamada yerini almaktadır. Bu çalışmada kültür ortamında MKH davranışına çoğalma, göç etme, farklanma ve yara iyileşmesi açılarından PB uygulamasının yapacağı etkiler araştırıldı.Gereç ve Yöntem: Dondurulmuş yağ dokusu kökenli MKH (YDMKH) hücre kültüre alınarak oniki kuyucuklu kültür tabağında 2.5x104hücre/cm2 olacak şekilde üretildi. Çoğalması MTT ile, göç etmesi çizik oluşturulması sonrası yara yerinin kapanması ile, farklanması kemik hücresi osteoblasta dönüştürülmesi ile incelendi. PB olarak NBL Probiotic Gold. Preparatı içersindeki 2.5x109 Enterococcus faecium, 2.5x109 lactobacillus acidophilus, 2.5x109lactobacillus rhamnosus, 2.5x109Bifidobacterium longum, 2.5x109Bifidobacterium bifidum bakterileri eklenip aynı ortamdaki MKH için davranış parametreleri açısından incelendi. PB ve MKH ilişkisi taramalı elektron mikroskobi ile de araştırıldı. Bulgular: PB eklenmesinin çoğalmayı hızlandırdığı, göç etmeyi arttırarak yara iyileşmesini çabuklaştırdığı ve osteoblastik kemiksi yapıya farklanmada olumlu katkısının oluştuğu saptandı. İnce yapı incelemesinde PB ile etkileşmiş MKH için daha canlı, daha çok tutunan ve daha aktif hücre morfolojisinde olduğu bulundu. Sonuç: Alınan sonuçlar kültür ortamına PB eklenmesinin MKH etkinliğini arttırdığını gösterdi. Deney hayvanı ile yapılacak çalışmalarda aynı olumlu etkinin görülmesinin klinik için yararlı olacağı düşünüldü.

Objectives: Although industrial products used as agricultural pesticides are considered safe, they are likely to lead to chronic problems due to their long-term effects. The neurotoxicity screening test (NST) is a method based on the inhibition of neurite extension of neurons that do not not die with toxic effects. In this study, we aimed to investigate the moderate neurotoxic effects and reveal the potential dangers of agricultural pesticides in vitro using NST. Methods: Cyantraniliprole, boscalid and spiromesifen were used as agricultural pesticides on the mouse neuroblastoma cell line N2a. Neurite extension of neurons was performed by taking them into the proliferation medium followed by the differentiation medium. Cell viability and proliferation were analyzed using the MTT test. The percentage of neurite inhibition was calculated by measuring neurite outgrowth by NST. Oxidative stress was analyzed by NOS staining with h-score and apoptosis was shown using the apoptotic index in TUNEL staining. Results: Cyantraniliprole, boscalid and spiromesifen at high concentrations caused neurite inhibition, decreased proliferation and reduced the viability of cultured neurons. These agricultural pesticides were found to be significantly moderate toxic for neurons by increasing oxidative stress and apoptosis. Conclusion: We conclude neurite inhibition may be important in early recognition for detecting and preventing the neurotoxic effect of pesticides, and NST is an important in vitro test that can predict the long-term effects of neurotoxic agents. In the present study, we observed cyantraniliprole, boscalid and spiromesifen had moderate neurotoxic effects in varying degrees using NST. This means that pesticides may behave toxic even in permissible limits for chronic exposure.

Abstract Background and aim Data on NOAC discontinuation patterns in Turkey are lacking. We conducted a subgroup analysis in ASPECT-NOAC study to determine anticoagulant discontinuation pattern in AF patients with recently initiated NOAC therapy. Methods ASPECT-NOAC was a national, multicenter, 12-month observational study conducted in 34 outpatient cardiology clinics of state, university, private, and research hospitals covering all geographic regions of Turkey. Adult AF patients who were under NOAC therapy for less than four months were enrolled. Patients who discontinued using their NOACs were recorded at the end of 12 months. A comparative analysis of patients with discontinuation of medication was conducted. Results This study included 991 non-valvular AF patients. NOAC continuation data were available for 854 patients. During study follow-up, 74 patients (8.7%) discontinued their NOAC medication. Mean age of these patients was 67.1±11.3 years old and 38 patients (51.4%) were female. Most commonly seen comorbidities were hypertension (66.2%) and coronary heart disease (39.2%). 29 patients (39.2%) had permanent (chronic) AF, followed by 26 patients (35.1%) with paroxysmal AF. Major reason for NOAC discontinuation was stated as physician request (n=46, 62%). Following reasons were patient request (n=17, 23%), other (n=9, 12%), and bleeding (n=2, 3%). Patients with NOAC discontinuation had a shorter duration of AF (21.7±41.7 vs 26.2±53.7 months, p=0.017). There was no significant difference of educational levels between medication discontinuation subgroups (p=0.637). Other baseline characteristics and patient disease and treatment awareness levels were similar with the patients who continued their medication. Of 74 patients, two patients died during the study because of cardiac failure. Conclusion NOAC continuity rate over 12 months was found to be high. NOAC discontinuation rate were higher in the patients with shorter duration of AF. Further studies with long-term follow-up detailing discontinuation reasons are warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was funded by Pfizer.

Objective: The aim of this study is to investigate the effects of low intensity pulsed ultrasound on orthodontic tooth movement in rats. Methods: For this study, 40 12-week-old adult male Wistar albino rats from the Animal Laboratory at Adnan Menderes University, Faculty of Medicine, were used. Rats were divided into four groups of ten. Group 1 was the untreated control group. In group 2, an orthodontic spring was used to move teeth. In groups 3 and 4, orthodontic treatment was combined with low intensity pulsed ultrasound at 16 J/cm 2 or 48 J/cm 2 , respectively, for 14 days. Tooth movement was measured on day 14. Serum bone alkaline phosphatase (BALP) and C-telopeptide of type I collagen (CTX-I) levels were analyzed biochemically. The number of osteoclasts, osteoblasts and inflammatory cells, capillary density and new bone formation was determined histologically. Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), vascular endothelial growth factor (VGEF) and transforming growth factor-β (TGF-β) were assessed using immunohistochemical staining. Results: BALP and CTX-I levels in group 4 were significantly higher than for group 1. Tooth movement and the number of osteoclasts, inflammatory cells, and capillary density in group 4 were significantly greater than for group 2. The intensity levels of RANKL and OPG in group 4 were significantly greater than for group 2. Conclusion: Ultrasound is noninvasive application and a promising therapy for accelerating bone remodeling during orthodontic tooth movement.