DNA and BSA Interaction Studies and Antileukemic Evaluation of Polyaromatic Thiosemicarbazones and Their Copper Complexes

Some ten million cancer deaths occurred in 2020, highlighting the fact that the search for new anticancer drugs remains extremely topical. In the search for new coordination compounds with relevant biological properties, the choice of a metal ion is important for the design of the complex. In this regard, copper plays a peculiar role, thanks to its distinct properties. Thiosemicarbazones are, analogously, a unique class of ligands because they are easily modifiable, and therefore, extremely versatile in terms of modulating molecular properties. In this work, we synthesized and characterized, by means of X-ray diffraction, four new naphthaldehyde and anthraldehyde thiosemicarbazone derivatives and their copper complexes to be used in interaction studies with biological systems. The objective was to evaluate the antileukemic activity of these compounds. Reactions of these ligands with Cu(II) salts produced unexpected oxidation products and the isolation of Cu(I) metal complexes. One ligand and its related Cu(I) complex, which is stable in physiological conditions, were subjected to in vitro biological tests (UV-Vis and CD titration). An important interaction with DNA and an affinity toward BSA were observed in FT-IR experiments. Preliminary in vitro biological tests against a histiocytic lymphoma cell line revealed an interestingly low IC50 value, i.e., 5.46 µM, for the Cu(I) comple

Sex Difference and Benzene Exposure: Does It Matter?

Sex-related biological differences might lead to different effects in women and men when they are exposed to risk factors. A scoping review was carried out to understand if sex could be a discriminant in health outcomes due to benzene. Studies on both animals and humans were collected. In vivo surveys, focusing on genotoxicity, hematotoxicity and effects on metabolism suggested a higher involvement of male animals (mice or rats) in adverse health effects. Conversely, the studies on humans, focused on the alteration of blood parameters, myeloid leukemia incidence and biomarker rates, highlighted that, overall, women had significantly higher risk for blood system effects and a metabolization of benzene 23-26% higher than men, considering a similar exposure situation. This opposite trend highlights that the extrapolation of in vivo findings to human risk assessment should be taken with caution. However, it is clear that sex is a physiological parameter to consider in benzene exposure and its health effects. The topic of sex difference linked to benzene in human exposure needs further research, with more numerous samples, to obtain a higher strength of data and more indicative findings. Sex factor, and gender, could have significant impacts on occupational exposures and their health effects, even if there are still uncertainties and gaps that need to be filled

Gallium(III)-pyridoxal thiosemicarbazone derivatives as nontoxic agents against Gram-negative bacteria

Many bacterial strains are developing mechanism of resistance to antibiotics, rendering last-resort antibiotics inactive. Therefore, new drugs are needed and in particular metal-based compounds represent a valid starting point to explore new antibiotic classes. In this study, we have chosen to investigate gallium(III) complexes for their potential antimicrobial activity against different strains of Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa which have developed different type of resistance mechanism, including the expression of beta-lactamases (NDM-1, ES beta L, or AmpC) or the production of biofilm. We studied a series of thiosemicarbabazones derived from pyridoxal, their related Ga(III) complexes, and the speciation in solution of the Ga(III)/ligand systems as a function of the pH. Proton dissociation constants and conditional stability constants of Ga(III) complexes were evaluated by UV/Vis spectroscopy, and the most relevant species at physiological pH were identified. The compounds are active against resistant Gram-negative strain with minimal inhibitory concentration in the mu M range, while no cytotoxicity was detected in eukaryotic cells

Autophagy and apoptosis: studies on the effects of bisthiosemicarbazone copper(II) complexes on p53 and p53-null tumour cell lines

A comparative study between two bisthiosemicarbazones, 2,3-butanedione bis(4,4-dimethyl-3-thiosemicarbazone) and 2,3-butanedione bis(2-methyl-3-thiosemicarbazone), and their copper(II) complexes is reported. The four compounds have been tested on leukemia cell line U937 and on adenocarcinoma cell line A549. The study includes cell viability, cell cycle, morphological changes, assessment of apoptosis, analysis of autophagy, measurement of reactive oxygen species (ROS) and of lipid peroxidation, protein determination, assessment of the expression of p53 and cellular uptake of metal complexes. Tests about the copper uptake under normoxic and hypoxic conditions were also carried out on solid tumour cell line A549. The four compounds under study elicit different effects on the two lines adopted as representatives of p53 and p53-null cells. The role of the metal is relevant and it is likely that the metal-mediated oxidative stress plays an essential role in the whole process. The mechanisms induced by these molecules differ not only as a function of cell line but also of dose. The responses include two distinct self-destructive processes, autophagy and apoptosis

A importância da pesquisa na formação do profissional da saúde

O processo educativo vivenciado em nossas universidades muitas vezes tem se sustentado numa prática docente tradicional, concebendo o aluno como receptor de conteúdos prontos e acabados. Esta prática dificulta o autêntico pensar, priorizando a reprodução em detrimento das idéias. Em contrapartida, o processo educativo que ultrapassa os limites de reprodução, fundamenta-se na criatividade e estimula a ação-reflexão, formando assim o profissional reflexivo. O estudante do curso de Medicina deve sentir-se desafiado a explorar e aprofundar seu conhecimento, a questionar e a reconstruir o conhecimento. A pesquisa como princípio pedagógico é uma das formas para que se concretize tal pressuposto. Este trabalho, uma pesquisa bibliográfica, pretende analisar as diretrizes que podem ser assumidas como referenciais para a formação do profissional de saúde deste século,identificar exigências que se colocam para um profissional da área de saúde e analisar a pesquisa como princípio pedagógico na formação e construção do conhecimento destes mesmos profissionais, Os teóricos escolhidos para fundamentar esta pesquisa são: Edgar Morin, Paulo Freire, Pedro Demo e Donald Schön.The education process experienced in our universities often has been sustained in a practice traditional teaching, designing the student as receiver of content ready and finished. This practice prevents the authentic thinking, prioritizing the reproduction at the expense of ideas. However, the education process that goes beyond the limits of reproduction, is based on the creativity and stimulates action-reflection, forming so professional reflective. The student of the course of Medicine must feel challenged to explore and deepen their knowledge, to question and rebuild knowledge. The research as a principle teaching is one way to come into being this assumption. This work, a bibliographic research, intends to examine the guidelines that can be taken as reference for the training of professional health of this century, identify requirements that arise for a professional in the area of health and analyze the survey as a teaching and training in construction the knowledge of these professionals, the theoretical chosen to support this research are: Edgar Morin, Paulo Freire, Pedro Demo and Donald Schön

Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers

Women with pathogenic germline mutations in BRCA1 and BRCA2 genes have an increased risk to develop breast and ovarian cancer. There is, however, a high interpersonal variability in the modality and timing of tumor onset in those subjects, thus suggesting a potential role of other individual’s genetic, epigenetic, and environmental risk factors in modulating the penetrance of BRCA mutations. MicroRNAs (miRNAs) are small noncoding RNAs that can modulate the expression of several genes involved in cancer initiation and progression. MiRNAs are dysregulated at all stages of breast cancer and although they are accessible and evaluable, a standardized method for miRNA assessment is needed to ensure comparable data analysis and accuracy of results. The aim of this review was to highlight the role of miRNAs as potential biological markers for BRCA mutation carriers. In particular, biological and clinical implications of a link between lifestyle and nutritional modifiable factors, miRNA expression and germline BRCA1 and BRCA2 mutations are discussed with the knowledge of the best available scientific evidence

Synthetic recovery of impulse propagation in myocardial infarction via silicon carbide semiconductive nanowires

: Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle. Conventional cardiac bypass graft and percutaneous coronary interventions allow reperfusion of the downstream tissue but do not counteract the bioelectrical alteration originated from the infarct area. Genetic, cellular, and tissue engineering therapies are promising avenues but require days/months for permitting proper functional tissue regeneration. Here we engineered biocompatible silicon carbide semiconductive nanowires that synthetically couple, via membrane nanobridge formations, isolated beating cardiomyocytes over distance, restoring physiological cell-cell conductance, thereby permitting the synchronization of bioelectrical activity in otherwise uncoupled cells. Local in-situ multiple injections of nanowires in the left ventricular infarcted regions allow rapid reinstatement of impulse propagation across damaged areas and recover electrogram parameters and conduction velocity. Here we propose this nanomedical intervention as a strategy for reducing ventricular arrhythmia after acute myocardial infarction