Synthesis, biological evaluation and in silico studies of novel thiadiazole-hydrazone derivatives for carbonic anhydrase inhibitory and anticancer activities.

Thiadiazole and hydrazone derivatives (5a-5i) were synthesized and their chemical structures were verified and described by 1H NMR, 13C NMR, and HRMS spectra. Three cancer cell lines (MCF-7, MDA, and HT-29) and one healthy cell line (L929) were used to test the cytotoxicity activity of synthesized compounds as well as their inhibitory activity against carbonic anhydrase I, II and IX isoenzymes. Compound 5d (29.74 µM) had a high inhibitory effect on hCA I and compound 5b (23.18 µM) had a high inhibitory effect on hCA II. Furthermore, compound 5i was found to be the most potent against CA IX. Compounds 5a-5i, 5b and 5i showed the highest anticancer effect against MCF-7 cell line with an IC50 value of 9.19 and 23.50 µM, and compound 5d showed the highest anticancer effect against MDA cell line with an IC50 value of 10.43 µM. The presence of fluoro substituent in the o-position of the phenyl ring increases the effect on hCA II, while the methoxy group in the o-position of the phenyl ring increases the activity on hCA I as well as increase the anticancer activity. Cell death induction was evaluated by Annexin V assay and it was determined that these compounds cause cell death by apoptosis. Molecular docking was performed for compounds 5b and 5d to understand their biological interactions. The physical and ADME properties of compounds 5b and 5d were evaluated using SwissADME.

Immunohistochemical profile of CD markers in experimental neural tube defect.

Neural tube defects (NTDs) are the second most common birth defects worldwide. Stem cells play a critical role in the mechanisms underlying NTDs. We established an experimental NTD model in rats using retinoic acid (RA). We used mesenchymal and hemopoietic stem cell markers to determine their distribution in the mesenchyme in and around the neuroepithelium during the embryonic and fetal periods in both cranial and caudal regions. Adult female rats were given RA on days 5 and 10 of gestation and olive oil was administered to the control group. On days 10.5 and 15.5, embryos in the experimental and control groups were removed from the uterus. Embryos were embedded in paraffin and serial sections of the cranial and caudal neural tube were examined. We found severe cranial and caudal defects including axial rotation in the experimental groups using histochemistry. We used CD44, CD56, CD73, CD90, CD105, CD271 antibodies as mesenchymal stem cell markers and CD14, CD45 as hemopoietic stem cell markers. More CD44, CD56, CD90, CD105 and CD14 were detected during the embryonic period than the fetal period. CD73 was more frequent during the fetal period, whereas CD271 and CD45 were not significantly different. When CD44, CD56, CD73, CD90, CD105, CD271 immunostaining was found, NTDs were decreased early and increased later. We found no significant difference between CD14 and CD45. Formation of NTDs was due to deterioration of the of the neuroepithelial and surrounding stem cells. One reason for the formation of NTDs is that stem cells may develop defective cell-cell or cell-matrix interactions.

Evaluation of the effects of different surface configurations on stability of miniscrews.

INTRODUCTION: The aim of this study was to analyze the effects of screw design and force application on the stability of miniscrews, using RTT, SEM, and histomorphometric analyses. MATERIALS AND METHODS: Eighty cylindrical, self-drilling, and Ti6Al4V alloy miniscrews (1,6 × 6 mm) were used. Four mini-screws were inserted in fibulas of each rabbit, and 115 G of force was immediately applied. Four miniscrews were inserted in the other fibula, on which no force was applied. Eight weeks after insertion, osseointegration between miniscrew and the surrounding bone was evaluated by the histomorphometric analyses, SEM, and RTT. Kruskal-Wallis and the paired t-tests were used for statistical analysis. RESULTS: Values obtained from Group I were significantly higher than those of the other loaded groups (P < .05). There were no differences in RTT scores among Groups II, III, and IV. Similar findings were also observed for unloaded mini-screws. There was no significant difference between Groups I and I(C), while the differences between loaded and unloaded controls for each miniscrew were statistically significant. CONCLUSIONS: Immediate loading of miniscrews does not impair screw stability. Also, the diameter of miniscrew and more frequent thread pitches have a positive effect on stability; however, length of miniscrews does not have a significant effect on the stability.

Glutathione S-transferase M1 and T1 polymorphisms in Turkish patients with varicocele.

Several studies have shown that high oxidative stress levels are associated with varicocele. The GST (glutathione S-transferase) family of genes is critical in the protection of cells from oxidative stress because they utilise as substrates a wide variety of products of oxidative stress. The objective of this study was to assess the relationship between genetic polymorphism in GST-M1 and GST-T1 and varicocele using 109 varicocele patients and 123 controls. Varicoceles were clinically graded as Grade 1, Grade 2 and Grade 3. GST-M1 and GST-T1 genes were determined by polymerase chain reaction. Although the GST-M1 null genotype was higher in Grade 3 than in Grade 1, 2 and controls, there were no statistical differences between control group and varicocele groups according to GST-M1 and GST-T1 null genotype. Men with varicocele do not have more GST-M1 and GST-T1 null polymorphisms than men without varicocele. Additional studies are needed to assess the exact mechanism by which the varicocele corresponds to elevated ROS levels.

A study on fuzzy C-means clustering-based systems in automatic spike detection.

In this study, different systems based on the fuzzy C-means (FCM) clustering algorithm are utilized for the detection of epileptic spikes in electroencephalogram (EEG) records. The systems are constructed as either single or two-stages. In contrast to single-stage systems, the two-stage system comprises a pre-classifier stage realized by a neural network. The FCM based two-stage system is also compared to a similar system implemented using the K-means clustering algorithm. The results imply that an FCM based two-stage system should be preferred as the spike detection system.