Centaurea mersinensis phytochemical composition and multi-dimensional bioactivity properties supported by molecular modeling.

Various studies conducted on Centaurea species indicate that the relevant plant is good source of bioactive phytochemicals. In this study, in vitro studies were used to determine bioactivity properties of methanol extract of Centaurea mersinensis - endemic species in Turkey - on extensive basis. Furthermore, the interaction of target molecules, identified for breast cancer and phytochemicals in the extract, was investigated via in silico analyses to support findings received in vitro. Scutellarin, quercimeritrin, chlorogenic acid and baicalin were primary phytochemicals in the extract. Methanol extract and scutellarin had higher cytotoxic effects against MCF-7 (IC50=22.17 µg/mL, and IC50=8.25 µM, respectively), compared to other breast cancer cell lines (MDA-MB-231, SKBR-3). The extract had strong antioxidant properties and inhibited target enzymes, especially α-amylase (371.69 mg AKE/g extract). The results of molecular docking indicate that main compounds of extract show high-strength bonding to the c-Kit tyrosine among target molecules identified in breast cancer, compared to other target molecules (MMP-2, MMP-9, VEGFR2 kinase, Aurora-A kinase, HER2). The tyrosinase kinase (1T46)-Scutellarin complex showed considerable stability in 150 ns simulation as per MD findings, and it was coherent with optimal docking findings. Docking findings and HOMO-LUMO analysis results corresponds with in vitro experiments. Medicinal properties of phytochemicals, which was determined to be suitable for oral use along with ADMET, were found to be within normal limits except for their polarity properties. In conclusion, in vitro and in silico studies indicated that the relevant plant yields promising results regarding its potential to develop novel and effective medicational products.Communicated by Ramaswamy H. Sarma.

Hypermagnesemia is associated with poor outcomes during hospitalization.

BACKGROUND: Hypermagnesemia is one of the vital electrolyte disturbances and is associated with such chronic conditions as cardiovascular, endocrinologic, renal diseases, and malignancy. AIM: This study evaluates the association between hypermagnesemia and clinical course in hospitalized patients. METHODS: This study was conducted at the University of Health Sciences Haseki Training and Research Hospital Internal Medicine Clinic. We evaluated a total of 3850 patients. 2130 patients have met the inclusion criteria were included in the study. Those who were discharged with healing were evaluated as having a good prognosis. Patients who died or were transferred to the intensive care unit (ICU) were defined as having a poor prognosis. We divided the patients' serum magnesium levels into four quartiles and examined the clinical course/conditions of the patients. RESULTS: Of 2130 patients, 1013 (51.9%) were female. The mean age of patients with poor prognoses (69.2 ± 14.9) was higher than those with good prognoses (59.7 ± 19.1). Hypermagnesemia (4th quartile) was detected in 61 (33.9%), and hypomagnesemia (1st quartile) was found in 42 (23.3%) patients out of 180 patients with poor clinical outcomes. It was statistically significant that hypermagnesemia was more common in patients with poor prognoses (p: 0.002). Chronic kidney disease (CKD) was diagnosed in 258 (53.3%) of 484 hypermagnesemia patients. Hypermagnesemia was found to be more common in patients with CKD, which was statistically significant (p: 0.003). CONCLUSIONS: Hypermagnesemia is associated with poor prognosis independent of comorbidities. Besides hypomagnesemia, hypermagnesemia should be considered a critical electrolyte imbalance.

Synthesis and biological evaluation of novel urea, thiourea and squaramide diastereomers possessing sugar backbone.

A series of novel chiral 14 urea, thiourea and squaramide stereoisomers possessing carbohydrate backbones as well as amide functional groups was synthesized and characterized by their, 1H NMR, 13C NMR, FT-IR, HRMS, optical rotation, and melting points. Their antiproliferative activities were investigated against HeLa and PC3 cell lines. The compounds 9, 11 and 12 showed better activities at 25 µM against PC3 cell line with respect to the standard 5-fluorouracil (5-FU). Especially, the compounds 9 and 11 showed higher activities than the standard 5-FU even at low concentration (5 µM) against HeLa cell line. IC50 results also confirm these activities. The compounds 9, 10 and 11 have the IC50 values of 1.10 µM, 1.51 µM and 1.02 µM, respectively while 5-FU has 2.51 µM. Moreover, their cytotoxicity tests have proven that their viabilities were in between 50% and 100%.

Does penile tourniquet application alter bacterial adhesion to rat urethral cells: an in vitro study.

PURPOSE: To investigate the effects of penile tourniquet (PT) application on bacterial adhesion to urothelium. METHODS: Fifty-six rats were allocated into control group (CG), sham group (SG), PT group (PTG). No intervention was applied in CG. A 5mm-length urethral repair was performed in SG and PTG. In PTG, a 10-min duration of PT was applied during the procedure and the tissue oxygenation monitor was used to adjust the same degree of ischemia in all subjects. Samples were examined for wound healing parameters and tissue levels of inflammatory markers, eNOS, e-selectin, and ICAM-1antibodies. The adhesion of Escherichia coli to urothelium was investigated with in vitro adhesion assay. RESULTS: Inflammation was higher and wound healing was worse in SG than CG and in PTG in comparison to CG and SG (p<0.05). The endothelial damage, as shown by eNOS expression, was significantly higher in PTG compared to CG and SG (p<0.05). The staining with ICAM-1 and e-selectin antibodies, showing increased inflammatory response to bacterial adhesion, was significantly higher in PTG compared to CG and SG (p<0.05). In vitro urethral cell proliferation was achieved only in CG and SG revealing significantly increased adhesion in SG compared to CG (p<0.05). The PT application caused endothelial corruption and prevented cell proliferation in cell culture. CONCLUSION: The PT application does not improve wound healing and increases bacterial adhesion molecules in penile tissue. The in vitro assays showed that PT causes severe endothelial damage and inhibits endothelial cell proliferation.