Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, (1)H NMR) methods. N'-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76 μM against colon cancer line HT-29 (ATCC, HTB-38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site.

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Objective We investigated the effects of bumetanide alone and in combination with dexamethasone on facial nerve regeneration in rats with facial paralysis. Study Design A prospective controlled animal study. Setting An animal laboratory. Subjects and Methods Facial paralysis was induced in 32 Wistar rats that we then divided into 4 groups: group 1, control; group 2, bumetanide; group 3, dexamethasone; group 4, bumetanide and dexamethasone. Electroneurography was performed 1, 2, and 4 weeks later, and nerve regeneration was evaluated by electron and light microscopy and Western blotting in week 4. Results Regarding the comparison between preoperative values and week 4, the latency difference in group 1 (1.25 milliseconds) was significantly higher than those of groups 2 to 4 (0.56, 0.34, and 0.10 milliseconds, respectively; P = .001). The latency increment in groups 2 and 3 was higher than that of group 4 ( P = .002 and P = .046) in week 4, whereas groups 2 and 3 did not differ significantly ( P = .291). Amplitude difference was not statistically significant from week 4 among all groups (all P > .05). The number of myelinated axons was significantly higher in all treatment groups than in the control group ( P = .001). Axon number and intensity were significantly higher in group 4 as compared with groups 2 and 3 ( P = .009, P = .005). Conclusion After primary neurorrhaphy, dexamethasone and bumetanide alone promoted nerve recovery based on electrophysiologic and histologic measures. Combination therapy was, however, superior.

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The first mixed ligand Mn (II) and Cd (II) complexes containing 4‐methoxy‐pyridine‐2‐carboxylic acid (4‐mpic) and 4,4′‐dimethyl‐2,2′‐bipyridine (dmbpy) were synthesized in this study. The geometric structures of [Mn(4‐mpic)2(dmbpy)] (complex 1) and [Cd(4‐mpic)2(dmbpy)] (complex 2) were determined by single crystal X‐Ray diffraction method. FT‐IR and UV–Vis spectra were also recorded to investigate vibrational and electronic properties of complexes 1 and 2. Density functional theory (DFT) calculations were also carried out to provide a deep understanding in geometric, spectroscopic, electronic and nonlinear optical (NLO) properties of complexes 1 and 2. The first‐order hyperpolarizibility (β) parameter calculated as 332.9736 × 10−30 esu demonstrated that complex 1 is an extremely promising candidate to NLO materials. Natural bond orbital (NBO) analysis not only verified the distorted octahedral geometries of central metal ions, but also found out the high‐energy interactions responsible for biological activities for complexes 1 and 2. Anti‐cancer activities of complexes 1 and 2 were tested on human breast carcinoma cell line MCF‐7 (ER and PR positive, HER2 negative) and the triple negative breast carcinoma cell line MDA‐MB 231 (ER, PR and HER2 negative). Dose–response relationship derived from MTT assays indicates that complexes 1 and 2 are showing concentration‐dependent effects, which could suggest a potential use for these drug combinations in cancer cell lines.

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BackgroundTelomeres are protective caps consisted of specific tandem repeats (5′-TTAGGG-3′). Shortening of telomeres at each cell division is known as “mitotic clock” of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex, which is a protein complex responsible from the preservation of cap structure, and loss or mutation of TRF2 results in DNA damage, senescence or apoptosis. Since cancer is frequently associated with aberrant cell cycle progression, defective DNA repair or apoptosis pathways, TRF2 could be one likely candidate for cancer therapy.Here we investigated the prognostic role of TRF2 levels in cervical cancer patients. Fold-induction rates were evaluated with respect to median values after real-time PCR analysis. Overall survival, distant disease-free and local recurrence-free survival rates were calculated using Kaplan-Meier long rank test.ResultsBoth five year overall- and disease-free survival rates were longer in patients with higher TRF2 expression compared to lower expression, but results were not statistically significant (69.2% vs 28.9%, respectively). Mean local recurrence-free survivals (LRF) were very close ( 58.6, CI: 44.3-72.9 vs 54.5, CI: 32.1-76.9 months) for high and low expressions, respectively. Cumulative proportion of LRF at the end of five year period was 76.9% for high and 57.1% for low TRF2 expression (P = 0.75). Statistically significant difference was found between survival ratios and Bcl-xL and p53 gene expressions, but not with TRF2. A respectable correlation between TRF2 expression and apoptosis along with distant metastasis was noted (P = 0.045 and 0.036, respectively). Additionally, high TRF2 expression levels had a positive impact in five year survival rate of stage IIIB-IVA patients (P = 0.04).ConclusionsOur results support the role of TRF2 in apoptosis and imply a positive relation with distant metastases and survival in advanced stage patients. The remarkable difference in survival periods of patients with different TRF2 expressions suggest that TRF2 may be a candidate factor to estimate survival for cervical cancer, a preliminary observation which should further be verified with a larger cohort.

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