Misoprostol-Induced Modification of the Notch Signaling Pathway in the Human Cervix

WOS: 000475782200005PubMed: 30278829The complex and multifactorial mechanisms that initiate and sustain the early labor process in the human uterus and cervix are still not well defined. Cervical maturation or ripening is likely to play a key role in preparing for birth. Prostaglandins have many different functions, including the regulation of uterine contractility and structure during pregnancy. The prostaglandin E1 analogue misoprostol is frequently used as a uterotonic and cervical ripening agent. Notch is a transmembrane receptor family responsible for basic functions such as cell survival, cell-cell communication, and differentiation and decidualization in pregnancy. However, our understanding of the effect of Notch signaling on the cervical ripening process is limited. This study was conducted in 20 pregnant women aged at 12 to 20 weeks of gestation undergoing medical abortion for fetal or maternal indications. True-Cut needle biopsies were taken from the anterior cervix 4 hours after oral ingestion of 200-mu g misoprostol or before the ingestion of misoprostol in the control group. Cervical expression of Notch receptors and ligands changed during the early phase of prostaglandin-induced preterm labor. Four hours after the administration of misoprostol, it was seen that N1 expression increased in muscle, while DLL1 and J2 expression increased in blood vessels, and N4 expression increased in macrophages. Knowing the mechanisms that initiate preterm birth is the most important step in planning the treatments and actions to prevent premature birth. As a signal that affects and perhaps directs preterm labor, Notch is prone to be an important actor in this process.Scientific and Technical Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215S942]The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Scientific and Technical Research Council of Turkey (TUBITAK) with Grant No. 215S942

The Role of Cholecystokinin in the Gastroprotective Effect of Apelin Against to Ischemia/Reperfusion-Induced Injury

WOS: 000453220100032…Akdeniz UniversityAkdeniz University [TDK-2015-593]Akdeniz University, Scientific Research Project No: TDK-2015-593

Antiandrogen abiraterone and docetaxel treatments affect Notch1, Jagged1 and Hes1 expressions in metastatic prostate cancer cells

© 2021 Elsevier Inc.Background: Prostate cancer is the most common cancer in men. A Notch signaling pathway is an important pathway in cell proliferation, differentiation, and fate. However, currently, the effects of abiraterone based-anti-androgene therapy and docetaxel, the most commonly used standard chemotherapy in prostate cancer treatment, on Notch signaling pathway are unknown. This study aimed to investigate the effects of abiraterone acetate and docetaxel on the expression of Notch1, Jagged1 and Hes1 in prostate cancer cell lines. Methods: In vitro effects of abiraterone acetate and docetaxel were examined on Notch1, Jagged1, and Hes1 expression in LNCaP and PC3 PCa cell lines by immunofluorescence, Western blot, and qRT-PCR. MTT proliferation assay was used to evaluate cell proliferation and survival. Results: We found that in the treatment of PC3 cells with abiraterone acetate, docetaxel, and their combination, only mRNA expressions of Notch1, Jagged1 and Hes1 were affected compared to control, but these expression differences were not observed in protein expression. In LNCaP cells, abiraterone acetate and the combination groups reduced Notch1 protein expression. All treatment groups did not alter Jagged1 expression compared to control, but significantly increased the Hes1 gene and protein expression. Conclusion: Our findings suggest that abiraterone and docetaxel treatments affects the expression of Notch signal pathway proteins. But these drugs especially cause significant upregulation in Hes1 expression in PCa cells. Therefore, co-application of Notch signaling inhibitors together with docetaxel and abiraterone chemotherapy, it was thought that decreased Hes1 expression could be stopped the deterioration of the prognosis of the patient

Zaštitni učinak dokozaheksaenske kiseline na želudac muških C57BL/6 miševa s Parkinsonovom bolešću izazvanom s MPTP

The purpose of this study was to detect gastric changes in Parkinson’s disease induced by 1-methyl-4-phenyl-1.2.3.6.-tetrahydropyridine (MPTP), and to investigate the protective effect of docosahexaenoic acid (DHA) against these changes in mice. The mice were divided into 4 groups (n=10 in per group) as control, DHA, Parkinson and DHA+Parkinson groups. DHA was administered by gavage for 30 days. On the 23rd day of gavage treatment, the animals of the Parkinson and DHA+Parkinson groups were intraperitoneally injected with MPTP. Seven days after the injection of MPTP, their locomotor activity, bradykinesia and rotarod performance were measured. Tyrosine hydroxylase expression in substantia nigra and the apoptotic index, the concentrations of tumor necrosis factor-α and histamine, and the number of mast cells in the stomach were evaluated. Administration of DHA significantly prevented the reduction in motor functions (P<0.001) and nigral TH neurons (P<0.05), and apoptosis (P<0.05), and an increase in TNF-α concentration (P<0.01) in the stomach. An increase in the number of mast cells in the stomach wall was observed in PD (P<0.001). DHA prevented the increase in the number of mast cells (P<0.05) and the histamine level (P<0.01) due to PD. As a result, MPTP administration in mice caused changes in the stomach as well as impairment in motor functions, and DHA was observed to reduce these changes.U radu je istražen zaštitni učinak dokozaheksaenske kiseline (DHA) na želučane promjene u muških miševa s Parkinsonovom bolešću (PD), izazvanom 1-metil-4-fenil-1.2.3.6.-tetrahidropiridinom (MPTP). C57BL/6 miševi su podijeljeni u četiri skupine (n = 10 po skupini): kontrolnu skupinu, skupinu DHA, skupinu Parkinson i skupinu DHA + Parkinson. DHA je primjenjivana pomoću sonde 30 dana. Dvadeset treći dan životinjama u skupinama Parkinson i DHA + Parkinson intraperitonealno je injiciran MPTP. Sedam dana poslije primjene MPTP-a izmjerena je lokomotorna aktivnost, bradikinezija i proveden rotarod-test. Procijenjeni su ekspresija tirozin-hidroksilaze (TH u substantia nigra), apoptotički indeks, koncentracije faktora tumorske nekroze alfa (TNF-α) i histamina te broj mastocita u želucu. Primjena DHA znakovito je prevenirala smanjenje motoričkih funkcija (P < 0,001) i TH neurona (P < 0,05) te apoptoze (P < 0,05), a povećala koncentraciju TNF-α (P < 0,01) u želucu. Porast broja mastocita u želučanoj stijenci utvrđen je u skupinama s PD (P < 0,001). DHA je prevenirala porast broja mastocita (P < 0,05) i razine histamina (P < 0,01) zahvaljujući PD-u. Zaključeno je da primjena MPTP-a u miševa uzrokuje promjene u želucu i motoričkim funkcijama te da DHA utječe na smanjenje tih promjena