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    Altered expression of Notch signaling, Tlr receptors, and surfactant protein expression after prostaglandin inhibition may be associated with the delayed labor in LPS-induced mice
    (Springer/Plenum Publishers, 2022) Avci, Sema; Kuscu, Nilay; Durkut, Begum; Kilinc, Leyla; Ustunel, Ismail; Celik-Ozenci, Ciler
    Purpose This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. Methods CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 mu g/100 mu l; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. Results Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. Conclusion In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.
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    Decreased IL-33 Expression in the Cervix in LPS-Induced Preterm Birth and the Potential Role of Mast Cells: A Murine Model
    (Wiley, 2025) Avci, Sema; Celik-Ozenci, Ciler; Kuscu, Nilay; Bektas, Nayce Ilayda
    Problem: In order to gain a deeper understanding of the mechanisms underlying LPS-mediated preterm birth, it is crucial to investigate the relationship between preterm birth and mast cells (MCs). Moreover, the role of antihistamines in inflammatory processes during pregnancy remains incompletely understood. Method of Study: CD-1 female mice were administered intrauterine lipopolysaccharide (LPS) via midline laparotomy to establish an inflammation-induced preterm birth model. The experimental groups (n = 6 per group) were formed as Nonpregnant and pregnant control, Sham, PBS, LPS, Cetirizine (CET) control, and two CET treatment groups (CET 10 mg/kg-low dose, and CET 20 mg/kg-high dose with LPS administration). Tissue samples were analyzed using immunohistochemistry and Western blot techniques. Results: Our findings suggest that MCs play a significant role in preterm birth, with LPS administration inducing MC dysfunction in the reproductive tract during pregnancy. Additionally, high doses of CET may support inflammatory responses. A particularly notable result was the reduction in interleukin-33 (IL-33) expression in the cervix during LPS-induced preterm birth. This suggests that IL-33 may serve as a potential biomarker for preterm birth in the cervix. Conclusions: The effects of CET during LPS-mediated preterm birth appear to be dose-dependent, warranting further exploration of their role in this context.
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    Evaluation of angiogenic apelin/apelin receptor axis in normal prostate, high grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma
    (Malaysian Journal Pathology, 2022) Soylu, Hakan; Unal, Betul; Aksu, Kubra; Avci, Sema; Caylan, Ahmet Ender; Ustunel, Ismail
    Introduction and Objectives: Prostate cancer is one of the most commonly diagnosed cancers in American men. Apelin is an endogenous peptide identified as the ligand of the G protein-associated apelin receptor. Apelin and apelin receptor have many tissues distribution and they participate in pathological processes, such as cancer. Apelin stimulates cancer angiogenesis. However, there are insufficient data in the literature regarding the role of apelin/apelin receptor in normal tissue, highgrade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma tissues. Therefore, this study aimed to investigate the apelin and apelin receptor expression levels in tissues of normal prostate tissue, high-grade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. Materials and Methods: In this study, 38 samples of patients undergoing radical prostatectomy were used. Among 38 samples; 20 patients were with prostatic adenocarcinoma, 18 patients were with high-grade prostatic intraepithelial neoplasia and adjacent normal prostatic tissue areas. The immunolocalisation of apelin and apelin receptor in these tissues were determined immunohistochemically. Results: Apelin and apelin receptor expressions were higher in prostatic adenocarcinoma than normal prostate tissue and high-grade prostatic intraepithelial neoplasia. Apelin receptor expression was also increased in high-grade prostatic intraepithelial neoplasia compared to normal tissue. Conclusion: Apelin and apelin receptor are increase in the process of prostate carcinogenesis. This increase may adversely affect the clinical course of prostate cancer patients by stimulating angiogenesis, which is important for invasion and metastasis in prostate cancer.
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    Evaluation of changes of apelin and apelin receptor (APJ) expression in cervix-uterus and placental axis in an LPS-induced labor model
    (Univ Basque Country Upv-Ehu Press, 2023) Avci, Sema; Golal, Ezgi; Acar, Nuray
    Although preterm birth is among the preventable causes of maternal and infant death, its mechanism has not yet been clarified. When evaluated in terms of the results, the psycho-social burden of mother-infant losses and the costs of rehabilitation, care, and treatment for postpartum sequelae are high. When evaluated in terms of its causes, infection/inflammation has an important place. Therefore, it is essential to understand the role of pro-and anti-inflammatory proteins in the process. In our study, apelin and apelin receptor (APJ) expression in the cervix-uterus and placental axis were evaluated at tissue and protein levels in pregnant and non-pregnant control, sham, PBS, and LPS groups in the infection model in which LPS induction was performed by midline laparotomy, in CD-1 mice. The evaluation of this axis regarding apelin and apelin receptor in the preterm birth model is new in the literature. Apelin is expressed more intensely in uterine epithelial cells than in the cervix. In the placenta, expression is more intense in the junctional zone compared to other zones. Apelin protein levels decrease significantly in the cervix and placenta whereas it increases in the uterus. While no change was observed in the expres- sion of the apelin receptor at the tissue and protein level in the cervix and uterus, it increased in both aspects in the placenta in the invasive procedure groups. We propose that the decrease in apelin protein due to LPS in the preterm delivery model may be related to the effort to compensate for the balance deteriorated in the pro-inflammatory direction with post-transitional modification at the tissue level. The tendency of apelin to increase with pregnancy has led to the conclusion that it is necessary for a healthy pregnancy. Although the apelin receptor does not change with inflammation, it is necessary to investigate the mechanisms associated with its stress and trauma-induced increase, since it increases in the invasive procedure group.
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    Expressions of Notch signalling pathway members during early pregnancy in mice
    (Springer, 2023) Acar, Nuray; Soylu, Hakan; Avci, Sema; Ustunel, Ismail
    Although pregnancy is initiated and maintained through highly complex mechanisms, it is essential to understand the events that occur before and during early pregnancy to understand a healthy implantation process. The Notch signal, thought to be involved in this process, is frequently the subject of research with its different aspects. To better understand the role of Notch signaling in the peri-implantation period of the mouse uterus, we investigated the state of expression and localization of Notch 3, Notch 4, Rbp-J, Hes1, Hes7, Hey2, HeyL, and Fbw7 in the uterus and implantation sites in early pregnancy. Balb/C mice were divided into groups D1, D4, D5, D6, and D8. For D5 and D6 groups, implantation sites were identified by intravenous injection of Chicago blue. IHC, WB, and QRT-PCR methods were used. Notch 3 was very strong positive on the 4th day of pregnancy. Notch 4 was highly expressed on days 4, 5, 6, and 8 of pregnancy when P-4 levels were high. Hes 1 level was at the lowest on the 4th day of pregnancy. Hes 7 protein expression gradually increased from D1 to D8 in the uteri and implantation sites. Hey 2 expression was at the highest level on the 1st and 4th days. Hey L expression was on the apical of the glands. Fbxw7 that expression was high on the 1st and 4th days of pregnancy. Notch signaling may play an essential role in regulating endometrial receptivity. In addition, our Hes7 results are new to the literature.
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    INDOMETHACIN CAN PROTECT PLACENTAL INFLAMMATION AND DELAY PRETERM BIRTH IN THE LPS-INDUCED PRETERM DELIVERY MODEL.
    (Elsevier Science Inc, 2021) Avci, Sema; Kuscu, Nilay; Durkut, Begum; Kilinc, Leyla; Ustunel, Ismail; Celik-Ozenci, Ciler
    [Abstract Not Available]