Tripeptide linked dispiro cyclotriphosphazene conjugates: Synthesis, molecular docking analysis of compounds binding within cancer cell line receptors and in vitro cytotoxic and genotoxic activities.

The novel dioxybiphenyl bridged-cyclotriphosphazenes (DPP) bearing tripeptide were synthesized and investigated for their molecular docking analysis, visualizing their binding profiles within various cancer cell line receptors and in vitro cytotoxic and genotoxic properties. The dipeptide compound (Tyr-Phe) was treated with various amino acids to obtain the tripeptide compounds (Tyr-Phe-Gly, Tyr-Phe-Ala, Tyr-Phe-Val, Tyr-Phe-Phe, and Tyr-Phe-Leu). These synthesized tripeptides were subsequently treated with DPP to obtain novel phosphazene compounds bearing tripeptide structures. As a result, the synthesis of target molecules with phosphazene compound in the center and biphenyl and tripeptide groups in the side arms was obtained for the first time in this study. Examining the cytotoxic studies in vitro of our newly synthesized compounds demonstrated the anticancer properties against four selected human cancer cell lines, including breast (MCF-7), ovarian (A2780), prostate (PC-3), and colon (Caco-2) cancer cells. The Comet Assay analysis determined that the cell death mechanism of most of the compounds with cytotoxic activity stemmed from the DNA damage mechanism. Among the compounds, the DPP-Tyr-Phe-Phe compound seems to have the best anticancer activity against the subjected cell lines (Except for A2780) with IC50 values equal to 20.18, 72.14, 12.21, and 5.17 µM against breast, ovarian, prostate, and colon cancer cell lines, respectively. For this reason, the molecular docking analysis was conducted for the DTPP compound to visualize its binding geometry and profile within the target enzyme's binding site associated with the specific cancer cell line. The analysis revealed that the DTPP derivative exhibited an optimal binding conformation and characteristics within the target enzyme's binding site, aligning well with the experimental data. Based on the data, these compounds are believed to be strong candidate molecules for both pharmaceutical and clinical applications.

Coumarin-Phosphazenes: Enhanced Photophysical Properties from Hybrid Materials.

Phosphazenes have drawn a great deal of interest over the past 20 years as a potentially useful building block for the fabrication of fluorescent materials. The main objective of this work is to explore novel derivatives produced by coumarins, a class of chemicals well-known for their photophysical importance, and cyclophosphazenes. UV absorbance, fluorescence emission, quantum yield, and lifetime measurements were conducted to comprehend the optical properties. Furthermore, single-crystal X-ray analysis and theoretical calculations were carried out to confirm the structure of the molecule. The obtained findings collectively confirm the commendable optical properties exhibited by the studied compounds. Moreover, a detailed study of the crystal packing arrangement of DPP-Et-Kum-Et compound crystallized in the P21/n monoclinic space group revealed the presence of stacking interactions between the nonplanar conjugated benzene rings of the coumarins and the rigid diphenyl groups attached to the phosphazene ring. The crystal structure of the DPP-Kum-Me-Me compound is mainly based on classical C-H···O intermolecular hydrogen bonding interactions with an average distance of 2.52 Å. Importantly, the calculated absorption spectra of the compounds are in close agreement with the experimental data, further supporting their interesting electronic properties. Given that the DPP-Et-Kum-Et and DPP-Kum-Et compounds have the theoretically lowest band gaps (4.31 and 4.30 eV, respectively), the activation energies of these compounds were determined by an impedance analyzer using dc conductance values measured at different temperatures. The calculated activation energies for DPP-Et-Kum-Et and DPP-Kum-Et are 104.49 and 100.92 meV, respectively. The results demonstrate that both theoretical and experimental calculations are in agreement with each other and that the DPP-Kum-Et compound has the lowest conductivity.

Expectant management vs. cerclage in cases with prolapsed or visible membranes in the second trimester: is 24 weeks gestation threshold critical?

OBJECTIVES: The aim of this study was to compare the efficacy of cervical cerclage with spontaneous follow-up strategy on pregnancy duration and neonatal outcomes in women with visible or prolapsed fetal membranes. METHODS: Patients who were referred to a single tertiary care centre between 1st January 2017 and 31st December 2022 were included in this comparative, retrospective cohort study. Patients were divided into two groups, those undergoing cerclage and those followed with no-cerclage. The range of pregnancy weeks for cerclage is between 18th and 27+6 weeks. RESULTS: A total of 106 cases were reviewed and nine were excluded. Based on shared decision making, cervical cerclage was performed in 76 patients (78.3 %) and 21 patients (21.6 %) were medically treated in no-cerclage group if there was no early rupture of the fetal membranes. The gestational age at delivery was 29.8 ± 6 [Median=30 (19-38)] weeks in the cerclage group and 25.8 ± 2.9 [Median=25 (19-32)] weeks in the no-cerclage group (p=0.004). Pregnancy prolongation was significantly longer in the cerclage group compared to the no-cerclage group (55 ± 48.6 days [Median=28 (3-138)] vs. 12 ± 17.9 days [Median=9 (1-52)]; p<0.001). Take home baby rate was 58/76 (76.3 %) in cerclage group vs. 8/21 (38 %) in no-cerclage group. In the post-24 week cerclage group the absolute risk reduction for pregnancy loss was 50 % (95 % CI=21.7-78.2). CONCLUSIONS: Cervical cerclage applied before and after 24 weeks (until 27+6 weeks) increased take home baby rate in women with visible or prolapsed fetal membranes without increasing adverse maternal outcome when compared with no-cerclage group.

Labiaplasty Outcomes and Complications in Turkish Women: A Multicentric Study.

INTRODUCTION AND HYPOTHESIS: We aimed to evaluate the outcomes, complication rates, and complication types of different labiaplasty techniques. METHODS: In this cross-sectional retrospective study, a total of 2,594 patients who underwent surgery owing to hypertrophy or asymmetry of the labium minus were retrospectively analyzed. Data were collected by individual interviews with 43 experts from different centers. The patients were between 18 and 50 years of age. During the interview information about the presence and nature of complications, and about concomitant or revision surgeries, were gathered. The surgeons who performed these surgeries were also questioned about their training and surgical experience. RESULTS: The most frequently observed complication was complete dehiscence, accounting for 29% of all complications. Complete dehiscence was most commonly seen after wedge resection (16 cases). The second most common complication was labium majus hematoma, accounting for 12.5% of all cases. Among the labiaplasty techniques, wedge resection had the highest complication rate at 3% (26 cases out of 753 patients). This was followed by composite labiaplasty at 1.2% (5 cases out of 395 patients), Z-plasty at 0.8% (1 case out of 123 patients), and trimming labiaplasty at 0.5% (7 cases out of 1,323 patients). CONCLUSION: Considering the heterogeneity and low quality of the existing studies on this subject, this study provides valuable information for surgeons practicing in this field. However, further research is clearly warranted as female genital aesthetic procedures are being performed with a steadily increasing trend.