Synthesis, Characterization, and Anticancer Activity of New N,N'-Diarylthiourea Derivative against Breast Cancer Cells.

The goal of the current study was to prepare two new homologous series of N,N'-diarylurea and N,N'-diarylthiourea derivatives to investigate the therapeutic effects of these derivatives on the methodologies of inhibition directed on human MCF-7 cancer cells. The molecular structures of the prepared derivatives were successfully revealed through elemental analyses, 1H-NMR, 13C-NMR and FT-IR spectroscopy. The cytotoxic results showed that Diarylthiourea (compound 4) was the most effective in suppressing MCF-7 cell growth when compared to all other prepared derivatives, with the most effective IC50 value (338.33 ± 1.52 µM) after an incubation period of 24 h and no cytotoxic effects on normal human lung cells (wi38 cells). Using the annexin V/PI and comet tests, respectively, treated MCF-7 cells with this IC50 value of the Diarylthiourea 4 compound displayed a considerable increase in early and late apoptotic cells, as well as an intense comet nucleus in comparison to control cells. An arrest of the cell cycle in the S phase was observed via flow cytometry in MCF-7 cells treated with the Diarylthiourea 4 compound, suggesting the onset of apoptosis. Additionally, ELISA research showed that caspase-3 was upregulated in MCF-7 cells treated with compound 4 compared to control cells, suggesting that DNA damage induced by compound 4 may initiate an intrinsic apoptotic pathway and activate caspase-3. These results contributed to recognizing that the successfully prepared Diarylthiourea 4 compound inhibited the proliferation of MCF-7 cancer cells by arresting the S cell cycle and caspase-3 activation via an intrinsic apoptotic route. These results, however, need to be verified through in vivo studies utilizing an animal model.

Synthesis of New Liquid-Crystalline Compounds Based on Terminal Benzyloxy Group: Characterization, DFT and Mesomorphic Properties.

The effect of the terminal benzyloxy group on the mesomorphic properties of liquid crystalline materials developed from rod-like Schiff base has been described. For this objective, a novel Schiff base liquid crystal family, specifically new series of Schiff base liquid crystals, namely, (E)-4-(alkyloxy)-N-(4-(benzyloxy)benzylidene)aniline, In, are prepared and investigated in detail. The length of the terminal alkyloxy chain (n) varies amongst the compounds in the series. Where n varies between 6, 8 and 16 carbons. At the other end of the compounds, benzyloxy moiety was attached. The molecular structures of all synthesized compounds were established using different spectroscopic techniques. The molecular self-assembly was explored using differential scanning calorimetry (DSC) and polarized optical microscope (POM). Depending on the length of the terminal alkyloxy chain, only one type of SmA phase with different stability was observed. The previously reported para-substituted systems and the present investigated compounds were compared and discussed. The calculated quantum chemical parameters were computationally correlated using the DFT method via the B3LYP 6-311G(d,p) basis set. The theoretical computations revealed that the length of the alkyl side chain influences the zero-point energy, reactivity and other estimated thermodynamic parameters of benzoyloxy/azomethine derivatives. Furthermore, the FMO energy analysis shows that molecule I16 have higher HOMO energies than the other compounds, and I6 has a much lower LUMO level than the rest.

Synthesis and characterization of new imine liquid crystals based on terminal perfluoroalkyl group.

New organic derivatives named, (E)-3(or4) -(alkyloxy)-N-{(trifluoromethyl)benzylidene}aniline, 1a-f, were synthesized and examined their liquid crystalline behaviors. FT-IR, 1H NMR, 13C NMR, 19F NMR, elemental analyses and GCMS were used to validate the prepared compounds' chemical structures. We used differential scanning calorimetry (DSC) and polarized optical microscopy (POM) to investigate the mesomorphic characteristics of the formed Schiff bases. All tested compounds of series 1a-c have mesomorphic behaviour of nematogenic temperature ranges while the group 1d-f show non-mesomorphic properties. Moreover, it was found that the enantiotropic N phases included all of the homologue 1a-c. Computational studies using DFT (density functional theory) validated the experimental mesomorphic behavior results. All the analyzed compounds had their dipole moments, polarizability, and reactivity characteristics explained. Theoretical simulations showed that as the length of the terminal chain is increased, the polarizability of the stuided compounds increases. Consequently, compounds 1a and 1d have the least polarizability.

Anaphylaxis and Related Events Following COVID-19 Vaccination: A Systematic Review.

The coronavirus disease 2019 (COVID-19), induced by the severe acute respiratory syndrome coronavirus 2, is responsible for a global pandemic following widespread transmission and death. Several vaccines have been developed to counter this public health crisis using both novel and conventional methods. Following approval based on promising efficacy and safety data, the AstraZeneca, Janssen, Moderna, Pfizer/BioNTech, and Sinovac vaccines have been administered globally among different populations with various reported side effects. Reports of life-threatening anaphylaxis following administration were of particular concern for both health care providers and the public. A systematic literature search using PubMed, Embase, Scopus, Web of Science, Science Direct, MedRxiv, and Lens.org databases identified relevant studies reporting anaphylaxis following vaccine administration. This systematic review includes 41 studies reporting anaphylaxis. A total of 7942 cases, including 43 deaths, were reported across 14 countries. Most cases occurred following the administration of the first dose. Importantly, the benefits of vaccination outweigh the risks of anaphylaxis. Subsequently, as populations continue to get vaccinated, it is important for health care providers to be able to recognize individuals at risk of developing anaphylaxis. Furthermore, they must be familiar with both the clinical hallmarks and treatment of anaphylactic reactions to minimize long-term sequalae and prevent death in vaccinated individuals.

Lymphadenopathy post-COVID-19 vaccination with increased FDG uptake may be falsely attributed to oncological disorders: A systematic review.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic that continues to cause numerous deaths to date. Four vaccines have been approved by the Food and Drug Administration as of July 2021 to prevent the transmission of COVID-19: Pfizer, Moderna, AstraZeneca, and Janssen. These vaccines have shown great efficacy and safety profile. One side effect that has been widely reported is post-COVID-19 vaccination lymphadenopathy. Due to the mimicry of the lymphadenopathy for metastases in some oncologic patients, there have been reports of patients who underwent biopsies that showed pathologic confirmation of benign reactive lymphadenopathy secondary to the COVID-19 vaccine. Therefore, understanding the incidence of lymphadenopathy post-COVID-19 vaccinations will help guide radiologists and oncologists in their management of patients, both present oncologic patients, and patients with concerns over their newly presenting lymphadenopathy. A systematic literature search was performed using several databases to identify relevant studies that reported lymphadenopathy post-COVID-19 vaccination. Our results revealed that several cases have been detected in patients undergoing follow-up fluorodeoxyglucose (FDG)-positron emission tomography-computerized tomography scans where lymph nodes ipsilateral to the vaccine injection site show increased uptake of FDG. Thus, knowledge of the incidence of lymphadenopathy may help avoid unnecessary biopsies, interventions, and changes in management for patients, especially oncologic patients who are at risk for malignancies.

Halting Tumor Progression via Novel Non-Hydroxamate Triazole-Based Mannich Bases MMP-2/9 Inhibitors; Design, Microwave-Assisted Synthesis, and Biological Evaluation.

Matrix metalloproteinases (MMPs) are key signaling modulators in the tumor microenvironment. Among MMPs, MMP-2 and MMP-9 are receiving renewed interest as validated druggable targets for halting different tumor progression events. Over the last decades, a diverse range of MMP-2/9 inhibitors has been identified starting from the early hydroxamic acid-based peptidomimetics to the next generation non-hydroxamates. Herein, focused 1,2,4-triazole-1,2,3-triazole molecular hybrids with varying lengths and decorations, mimicking the thematic features of non-hydroxamate inhibitors, were designed and synthesized using efficient protocols and were alkylated with pharmacophoric amines to develop new Mannich bases. After full spectroscopic characterization the newly synthesized triazoles tethering Mannich bases were subjected to safety assessment via MTT assay against normal human fibroblasts, then evaluated for their potential anticancer activities against colon (Caco-2) and breast (MDA-MB 231) cancers. The relatively lengthy bis-Mannich bases 15 and 16 were safer and more potent than 5-fluorouracil with sub-micromolar IC50 and promising selectivity to the screened cancer cell lines rather than normal cells. Both compounds upregulated p53 (2-5.6-fold) and suppressed cyclin D expression (0.8-0.2-fold) in the studied cancers, and thus, induced apoptosis. 15 was superior to 16 in terms of cytotoxic activities, p53 induction, and cyclin D suppression. Mechanistically, both were efficient MMP-2/9 inhibitors with comparable potencies to the reference prototype hydroxamate-based MMP inhibitor NNGH at their anticancer IC50 concentrations. 15 (IC50 = 0.143 µM) was 4-fold more potent than NNGH against MMP-9 with promising selectivity (3.27-fold) over MMP-2, whereas 16 was comparable to NNGH. Concerning MMP-2, 16 (IC50 = 0.376 µM) was 1.2-fold more active than 15. Docking simulations predicted their possible binding modes and highlighted the possible structural determinants of MMP-2/9 inhibitory activities. Computational prediction of their physicochemical properties, ADMET, and drug-likeness metrics revealed acceptable drug-like criteria.

Study of force loss due to friction comparing two ceramic brackets during sliding tooth movement.

OBJECTIVE: To compare the percentage of force loss generated during canine sliding movements in newly introduced ceramic brackets with metal brackets. MATERIALS AND METHODS: Two types of ceramic brackets, namely polycrystalline alumina (PCA) ceramic brackets (Clarity Advanced) and monocrystalline alumina (MCA) ceramic brackets (Inspire Ice) were compared with stainless steel (SS) brackets (Victory Series). All bracket groups (n = 5 each) were for the maxillary canines and had a 0.018-inch slot size. The brackets were mounted on an Orthodontic Measurement and Simulation System (OMSS) to simulate the canine retraction movement into the first premolar extraction space. Using elastic ligatures, 0.016 × 0.022″ (0.40 × 0.56 mm) stainless steel archwires were ligated onto the brackets. Retraction force was applied via a nickel-titanium coil spring with a nearly constant force of approximately 1 N. The OMSS measured the percentage of force loss over the retraction path by referring to the difference between the applied retraction force and actual force acting on each bracket. Between group comparisons were done with one-way analysis of variance. RESULTS: The metal brackets revealed the lowest percentage of force loss due to friction, followed by the PCA and MCA ceramic bracket groups (67 ± 4, 68 ± 7, and 76 ± 3 %, respectively). There was no significant difference between SS and PCA brackets (p = 0.97), but we did observe significant differences between metal and MCA brackets (p = 0.03) and between PCA and MCA ceramic brackets (p = 0.04). CONCLUSION: PCA ceramic brackets, whose slot surface is covered with an yttria-stabilized zirconia-based coating exhibited frictional properties similar to those of metal brackets. Frictional resistance resulted in an over 60 % loss of the applied force due to the use of elastic ligatures.