Targeting lysosomes by design: novel -acridine thiosemicarbazones that enable direct detection of intracellular drug localization and overcome P-glycoprotein (Pgp)-mediated resistance.

Innovative -acridine thiosemicarbazones (NATs) were designed along with their iron(iii), copper(ii), and zinc(ii) complexes. Lysosomal targeting was promoted by specifically incorporating the lysosomotropic Pgp substrate, acridine, into the thiosemicarbazone scaffold to maintain the tridentate N, N, S-donor system. The acridine moiety enables a significant advance in thiosemicarbazone design, since: (1) it enables tracking of the drugs by confocal microscopy using its inherent fluorescence; (2) it is lysosomotropic enabling lysosomal targeting; and (3) as acridine is a P-glycoprotein (Pgp) substrate, it facilitates lysosomal targeting, resulting in the drug overcoming Pgp-mediated resistance.

Isosteric Replacement of Sulfur to Selenium in a Thiosemicarbazone: Promotion of Zn(II) Complex Dissociation and Transmetalation to Augment Anticancer Efficacy.

We implemented isosteric replacement of sulfur to selenium in a novel thiosemicarbazone (PPTP4c4mT) to create a selenosemicarbazone (PPTP4c4mSe) that demonstrates potentiated anticancer efficacy and selectivity. Their design specifically incorporated cyclohexyl and styryl moieties to sterically inhibit the approach of their Fe(III) complexes to the oxy-myoglobin heme plane. Importantly, in contrast to the Fe(III) complexes of the clinically trialed thiosemicarbazones Triapine, COTI-2, and DpC, the Fe(III) complexes of PPTP4c4mT and PPTP4c4mSe did not induce detrimental oxy-myoglobin oxidation.

Multi-modal mechanisms of the metastasis suppressor, NDRG1: Inhibition of WNT/β-catenin signaling by stabilization of protein kinase Cα.

The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), inhibits pro-oncogenic signaling in pancreatic cancer (PC). This investigation dissected a novel mechanism induced by NDRG1 on WNT/β-catenin signaling in multiple PC cell types. NDRG1 overexpression decreased β-catenin and downregulated glycogen synthase kinase-3β (GSK-3β) protein levels and its activation.

Differential transmetallation of complexes of the anti-cancer thiosemicarbazone, Dp4e4mT: effects on anti-proliferative efficacy, redox activity, oxy-myoglobin and oxy-hemoglobin oxidation.

The di-2-pyridylthiosemicarbazone (DpT) analogs demonstrate potent and selective anti-proliferative activity against human tumors. The current investigation reports the synthesis and chemical and biological characterization of the Fe(iii), Co(iii), Ni(ii), Cu(ii), Zn(ii), Ga(iii), and Pd(ii) complexes of the promising second generation DpT analog, di-2-pyridylketone-4-ethyl-4-methyl-3-thiosemicarbazone (Dp4e4mT). These studies demonstrate that the Dp4e4mT Co(iii), Ni(ii), and Pd(ii) complexes display distinct biological activity those with Cu(ii), Zn(ii), and Ga(iii) regarding anti-proliferative efficacy against cancer cells and a detrimental off-target effect involving oxidation of oxy-myoglobin (oxy-Mb) and oxy-hemoglobin (oxy-Hb).

Steric Blockade of Oxy-Myoglobin Oxidation by Thiosemicarbazones: Structure-Activity Relationships of the Novel PPP4pT Series.

The di-2-pyridylketone thiosemicarbazones demonstrated marked anticancer efficacy, prompting progression of DpC to clinical trials. However, DpC induced deleterious oxy-myoglobin oxidation, stifling development. To address this, novel substituted phenyl thiosemicarbazone (PPP4pT) analogues and their Fe(III), Cu(II), and Zn(II) complexes were prepared.

Quantification of Bioactive Metabolites Derived from Cell-Free Supernatant of Pediococcus acidilactici and Screening their Protective Properties in Frankfurters.

The specific aims of the current study were to determine and quantify the bioactive compounds derived from the cell-free supernatant (CFS) of Pediococcus acidilactici and screen their protective effect in frankfurters by applying an edible coating. This was achieved by immersing the peeled frankfurters in the CFS (CFS: 50% and 100%) alone or in combination with chitosan (CH: 0.5% and 1%) solutions for 3 min.

Inhibitory effect of bioactive compounds derived from freeze-dried paraprobiotic of Pediococcus acidilactici against food-borne pathogens: In-vitro and food model studies.

It was aimed to assess the antimicrobial potential of lyophilized/freeze-dried paraprobiotic (LP) of P. acidilactici against some food-borne pathogens under in-vitro conditions and food model, and determination of bioactive compounds that contribute to the antimicrobial activity of LP. For this purpose, minimum inhibitory concentration (MIC), inhibition zones were determined against Listeria monocytogenes, Salmonella Typhimurium and Escherichia coli O157:H7.

Final-year medical student mental wellness during preparation for the examination for specialty in Turkey: a cross-sectional survey study.

Background: In Turkey, most final-year medical students prepare for the Examination for Specialty in Medicine in a high-stress environment. To the best of our knowledge, this is the first study on final-year medical student general psychological distress during preparation for the Examination for Specialty in Turkey. We aim to evaluate psychological distress and understand the variables associated with depression, anxiety, and stress levels among final-year medical students preparing for the Examination for Specialty.

Designing Tailored Thiosemicarbazones with Bespoke Properties: The Styrene Moiety Imparts Potent Activity, Inhibits Heme Center Oxidation, and Results in a Novel "Stealth Zinc(II) Complex".

A novel, potent, and selective antitumor agent, namely ()-3-phenyl-1-(2-pyridinyl)-2-propen-1-one 4,4-dimethyl-3-thiosemicarbazone (PPP44mT), and its analogues were synthesized and characterized and displayed strikingly distinctive properties. This activity was mediated by the inclusion of a styrene moiety, which through steric and electrochemical mechanisms prevented deleterious oxy-myoglobin or oxy-hemoglobin oxidation relative to other potent thiosemicarbazones, i.e.

Multi-target activity of copper complexes: Antibacterial, DNA binding, and molecular docking with SARS-CoV-2 receptor.

A series of pendant-armed mixed-ligand copper(II) complexes of the type [CuL(diimine)] (1-6) have been synthesized by the reaction of pendant-armed ligands N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)benzamide (HL), N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-4-nitrobenzamide (HL) and N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-3,5-dinitrobenzamide (HL) with diimine = 2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen) in the presence of copper(II) chloride and analyzed using various spectroscopic methods. All the spectroscopic results support that the complexes adopt a pentagonal-bipyramidal shape around the copper ion. Gram-positive and Gram-negative bacteria were used to test all the complexes for antibacterial activity and all the complexes had greater potency against gram-negative pathogens.

Radiomics-based machine learning models for prediction of medulloblastoma subgroups: a systematic review and meta-analysis of the diagnostic test performance.

Background: Medulloblastomas are a major cause of cancer-related mortality in the pediatric population. Four molecular groups have been identified, and these molecular groups drive risk stratification, prognostic modeling, and the development of novel treatment modalities. It has been demonstrated that radiomics-based machine learning (ML) models are effective at predicting the diagnosis, molecular class, and grades of CNS tumors.

Three-dimensional digital evaluation of tooth symmetry and volume in patients with missing and peg-shaped maxillary lateral incisors.

Introduction: This study aimed to evaluate the 3-dimensional tooth crown symmetry and the crown volumes of maxillary and mandibular teeth in patients with unilateral or bilateral missing or peg-shaped maxillary lateral incisors.

Methods: Six groups were established for the possible clinical variations in patients with unilateral missing or peg-shaped maxillary lateral incisors, bilateral presence of these tooth anomalies, and a control group (CG) with normal lateral incisors. The study was conducted on digital dental models of 132 patients.

New oxovanadium(IV) complexes overcame drug resistance and increased in vitro cytotoxicity by an apoptotic pathway in breast cancer cells.

In order to examine the anticancer potential of oxovanadium(IV) complexes with thiosemicarbazone, two new complexes were prepared starting from 2-thenoyltrifluoroacetone-S-methylthiosemicarbazone. The complexes with tetradentate thiosemicarbazone ligand were characterized by elemental analysis, IR, ESI MS, and single-crystal X-ray diffraction analysis. Cytotoxicity on breast cancer cells, MDA-MB-231 and MCF-7, was determined by MTT assay.

Characterization of lactic acid bacteria postbiotics, evaluation in-vitro antibacterial effect, microbial and chemical quality on chicken drumsticks.

The aims of this study were to characterize postbiotics, and to evaluate their antibacterial effects in-vitro and on chicken drumsticks. Postbiotics [Pediococcus. acidilactici (PA), Latilactobacillus sakei/Staphylococcus xylosus (LS)] exhibited strong antioxidant activity, and their total phenolic contents were found as 2952.

Impact of chitosan embedded with postbiotics from Pediococcus acidilactici against emerging foodborne pathogens in vacuum-packaged frankfurters during refrigerated storage.

The objective of the study was to carry out characterization of postbiotics from Pediococcus acidilactici and to assess their efficacy (50% and 100%) in combination with chitosan (0.5 and 1%) against Escherichia coli O157:H7, Salmonella Typhimurium, Listeria monocytogenes on frankfurters during refrigerated storage for 35 days. High amounts of total phenolic content (1708.

New thiosemicarbazone-based Zinc(II) complexes. In vitro cytotoxicity competing with cisplatin on malignant melanoma A375 cells and its relation to neuraminidase inhibition.

New thiosemicarbazone-based zinc(II) complexes were synthesized to study their cytotoxicity on A375 malignant melanoma cells. The complexes containing salicylidene (Zn1a), 3-methoxy-salicylidene (Zn1b) or 4-methoxy-salicylidene (Zn1c) moiety were characterized by analytical and spectroscopic methods. Anticancer potential of the complexes was determined by MTT test and HUVEC endothelial cells line was used to comprehend the effect on normal cells.

The iron(III) and nickel(II) complexes with tetradentate thiosemicarbazones. Synthesis, experimental, theoretical characterization, and antiviral effect against SARS-CoV-2.

The discovery of new inhibitors that can be used in the treatment of viral diseases, including Covid-19, is an area open to research, and there is a need for innovative compounds with increased efficiency that provide inhibition by suppressing enzyme, and receptor mechanisms. The iron(III) and nickel(II) complexes were synthesized by template condensation of 4-methoxy-salicylaldehyde with S-methylthiosemicarbazone derivatives of 1,1,1-trifluoroacetylacetone (for ) and methylacetoacetate (for ). The complex structures having NO-chelating thiosemicarbazidato ligand were identified by analytical, spectroscopic, and X-ray crystallography results.

Characterization of Pediococcus acidilactici postbiotic and impact of postbiotic-fortified chitosan coating on the microbial and chemical quality of chicken breast fillets.

This study was carried out to characterize antioxidant activity, total phenolic content, and the phenolic and flavonoids profile of postbiotic of Pediococcus acidilactici and to evaluate the effects of postbiotics (10% and 50%) alone and in combination with chitosan coating (1%) on the microbial and chemical quality of chicken breast fillets during storage at 4 °C. Antioxidant activity and total phenolic content of the postbiotics were found to be 1291.02 ± 1.

Iron(III) and nickel(II) complexes of tetradentate thiosemicarbazones: Synthesis, structure, cytotoxicity, and lipophilicity.

Eighteen of the iron(III) and nickel(II) complexes with tetradentate thiosemicarbazidato ligands were synthesized and described, by analytical and spectroscopic methods. Two complexes as an example to the iron and nickel centered ones were crystallographically analyzed to confirm the molecular structures. Cytotoxic effects of the complexes on K562 chronic myeloid leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

Structural analysis and biological functionalities of iron(III)- and manganese(III)-thiosemicarbazone complexes: in vitro anti-proliferative activity on human cancer cells, DNA binding and cleavage studies.

One iron(III) and two manganese(III) complexes based on thiosemicarbazone were synthesized and characterized using analytical and spectroscopic data. The crystallographic analysis showed the square pyramid structures of the complexes. Electronic spectra analysis was performed to determine the nature of the interaction between the complexes and calf thymus DNA (CT-DNA).

Novel palladium (II) complexes with tetradentate thiosemicarbazones. Synthesis, characterization, in vitro cytotoxicity and xanthine oxidase inhibition.

In vitro cytotoxicity and xanthine oxidase inhibition capabilities were investigated for five palladium (II) chelate complexes. The palladium complexes were synthesized by starting from S-alkyl-thiosemicarbazones where the alkyl component is methyl, ethyl, propyl or butyl. The solid complexes are characterized by elemental analysis and spectroscopic techniques (UV-visible, IR and 1H NMR).

Development of the perceived stigma scale and the concealment of epilepsy scale for the Turkish population.

The aim of this study was to develop two culture-specific scales to measure the level of felt stigma, and level of concealment of Turkish adult people with epilepsy (PWE). For this purpose, a 10-item felt-stigma scale and a 17-item disclosure of epilepsy scale were developed and then applied to 200 adult PWE. After item and factor analyses of the stigma scale, the 10 items with a one-factor solution explained 45.