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A inteligência artificial é cada vez mais utilizada pelos médicos para o auxílio no diagnóstico de doenças. Essa tecnologia, por suas características, é capaz de gerar inúmeros benefícios, tais como permitir que procedimentos de diagnóstico médico sejam realizados de forma invariavelmente mais célere e normalmente mais precisa. Contudo, essa tecnologia é igualmente capaz de fomentar vieses cognitivos e interferir negativamente no processo de tomada de decisão do médico, podendo assim contribuir para a ocorrência de erros de diagnóstico. O presente trabalho apresenta justamente a possibilidade de ocorrência desses erros de diagnóstico decorrentes do viés da automação e o papel da responsabilidade civil do médico frente a essa nova problemática, analisando as diversas variáveis potencialmente ocorrentes. Utiliza-se a metodologia de pesquisa básica quanto à finalidade, descritiva quanto aos objetivos, qualitativa quanto à abordagem, dedutiva e dialética quanto ao método, e bibliográfica quanto ao procedimento.

Efeitos de borda são modificações nos parâmetros físicos, químicos e biológicos observados na área de contato da margem da floresta com a matriz circundante, sendo a disponibilidade de luz um fator crucial para o seu desencadeamento. O objetivo do estudo foi avaliar a influência da disponibilidade de luz sobre a abundância de espécies pioneiras no interior de fragmentos de uma floresta tropical submontana, no município de Wenceslau Guimarães, Bahia. Os resultados mostram uma redução da abundância de espécies pioneiras com o aumento da distância em relação à borda, sendo explicada pelo aumento do adensamento foliar, e conseqüente diminuição da disponibilidade de luz a partir de 30 metros de distância da borda. O entendimento deste padrão se mostra satisfatório ao explicar a distribuição de plantas pioneiras em paisagens fragmentadas, sendo útil no desenvolvimento de estratégias de gestão visando o manejo adequado da paisagem.Edge effects are changes in physical, chemical and biological parameters observed in the area of contact of the forest edge with the surrounding matrix. Light availability is the crucial trigger factor. The aim of this study was to assess the influence of light availability on abundance of pioneer plant species in a fragment of a tropical submontane forest, in the municipality of Wenceslau Guimarães, Bahia, Brazil. The results showed reduced abundance of pioneer species as edge distance increased. This can be explained by increased leaf density, and consequently reduction of light availability as of 30 meters from the edge in the various forest strata. This pattern explains the distribution of pioneer plants in fragmented landscapes, and is useful in the development of management strategies such as proper management of the landscape.

Background & Aims: Metallothionein-3 (hMT3) is a structurally unique member of the metallothioneins family of low-mass cysteine-rich proteins. hMT3 has poorly characterized functions, and its importance for hepatocellular carcinoma (HCC) cells has not yet been elucidated. Therefore, we investigated the molecular mechanisms driven by hMT3 with a special emphasis on susceptibility to sorafenib., Methods: Intrinsically sorafenib-resistant (BCLC-3) and sensitive (Huh7) cells with or without up-regulated hMT3 were examined using cDNA microarray and methods aimed at mitochondrial flux, oxidative status, cell death, and cell cycle. In addition, in ovo/ex ovo chick chorioallantoic membrane (CAM) assays were conducted to determine a role of hMT3 in resistance to sorafenib and associated cancer hallmarks, such as angiogenesis and metastastic spread. Molecular aspects of hMT3-mediated induction of sorafenib-resistant phenotype were delineated using mass-spectrometry-based proteomics., Results: The phenotype of sensitive HCC cells can be remodeled into sorafenib-resistant one via up-regulation of hMT3. hMT3 has a profound effect on mitochondrial respiration, glycolysis, and redox homeostasis. Proteomic analyses revealed a number of hMT3-affected biological pathways, including exocytosis, glycolysis, apoptosis, angiogenesis, and cellular stress, which drive resistance to sorafenib., Conclusions: hMT3 acts as a multifunctional driver capable of inducing sorafenib-resistant phenotype of HCC cells. Our data suggest that hMT3 and related pathways could serve as possible druggable targets to improve therapeutic outcomes in patients with sorafenib-resistant HCC., (© 2024. The Author(s).)

Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a widely used cytostatic agent; however, it tends to promote kidney and liver disease, which are a major signs of drug-induced toxicity. Platinum compounds are often presented as alternative therapeutics and subsequently easily dispersed in the environment as contaminants. Due to the major roles of the liver and kidneys in removing toxic materials from the human body, we performed a comparative study of the amino acid profiles in chicken liver and kidneys before and after the application of CDDP and platinum nanoparticles (PtNPs-10 and PtNPs-40). The treatment of the liver with the selected drugs affected different amino acids; however, Leu and Arg were decreased after all treatments. The treatment of the kidneys with CDDP mostly affected Val; PtNPs-10 decreased Val, Ile and Thr; and PtNPs-40 affected only Pro. In addition, we tested the same drugs on two healthy cell lines, HaCaT and HEK-293, and ultimately explored the amino acid profiles in relation to the tricarboxylic acid cycle (TCA) and methionine cycle, which revealed that in both cell lines, there was a general increase in amino acid concentrations associated with changes in the concentrations of the metabolites of these cycles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mitrevska, Cernei, Michalkova, Rodrigo, Sivak, Heger, Zitka, Kopel, Adam and Milosavljevic.)

Metallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.

The efficiency of cisplatin (CDDP) is significantly hindered by the development of resistance during the treatment course. To gain a detailed understanding of the molecular mechanisms underlying the development of cisplatin resistance, we comparatively analyzed established a CDDP-resistant neuroblastoma cell line (UKF-NB-4 CDDP ) and its susceptible parental cells (UKF-NB-4). We verified increased chemoresistance of UKF-NB-4 CDDP cells by analyzing the viability, induction of apoptosis and clonal efficiency. To shed more light on this phenomenon, we employed custom cDNA microarray (containing 2234 probes) to perform parallel transcriptomic profiling of RNA and identified that 139 genes were significantly up-regulated due to CDDP chemoresistance. The analyses of molecular pathways indicated that the top up-regulation scoring functions were response to stress, abiotic stimulus, regulation of metabolic process, apoptotic processes, regulation of cell proliferation, DNA repair or regulation of catalytic activity, which was also evidenced by analysis of molecular functions revealing up-regulation of genes encoding several proteins with a wide-spectrum of enzymatic activities. Functional analysis using lysosomotropic agents chloroquine and bafilomycin A1 validated their potential to re-sensitize UKF-NB-4 CDDP cells to CDDP. Taken together, the identification of alterations in specific genes and pathways that contribute to CDDP chemoresistance may potentially lead to a renewed interest in the development of novel rational therapeutics and prognostic biomarkers for the management of CDDP-resistant neuroblastoma.

Background: Metallothioneins (MTs) constitute a family of evolutionary conserved low molecular weight proteins with small variations in their amino acid sequences. They play a role in the regulation of trace metals metabolism, in the detoxification of heavy metal ions and in mechanisms controlling growth, differentiation and proliferation of cells., Objectives: The aim of this study was to evaluate the human and rabbit MTs purity and characterization using advanced analytical approaches. Due to the common use of MT from rabbit liver as a model protein, the properties of the rabbit and human MTs were compared., Material and Methods: Capillary electrophoresis (CE), matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and Brdicka reaction were used for human and rabbit MTs characterization., Results: In chip CE analysis, changes in the range of 5-8 kDa corresponding to the MT monomer, as well as some peaks of 13-14 kDa corresponding to dimers in both species, were observed. Using MALDI-MS, rabbit (MT-2D) and human (MT-1A, MT-1G, MT-1G + Cd and MT-2A) MTs were identified. In the Brdicka reaction analysis, a lower concentration of MTs from both organisms coincided with a decrease in the signal corresponding to MT level (Cat2). However, human MT gave higher Cat2 peak than the same concentration (0.025 mg/mL) of rabbit MT., Conclusions: The applied methods allowed for the characterization of MTs and gave complementary information about MT isoforms. Altered electrochemical activity of human and rabbit MTs, despite the same number of -sulfhydryl (-SH) groups, was observed, which may be due to different availability of MT cysteinyl groups.

Background: Sarcosine is a widely discussed oncometabolite of prostate cells. Although several reports described connections between sarcosine and various phenotypic changes of prostate cancer (PCa) cells, there is still a lack of insights on the complex phenomena of its effects on gene expression patterns, particularly in non-malignant and non-metastatic cells., Methods: To shed more light on this phenomenon, we performed parallel microarray profiling of RNA isolated from non-malignant (PNT1A), malignant (22Rv1), and metastatic (PC-3) prostate cell lines treated with sarcosine. Microarray results were experimentally verified using semi-quantitative-RT-PCR, clonogenic assay, through testing of the susceptibility of cells pre-incubated with sarcosine to anticancer agents with different modes of actions (inhibitors of topoisomerase II, DNA cross-linking agent, antimicrotubule agent and inhibitor of histone deacetylases) and by evaluation of activation of executioner caspases 3/7., Results: We identified that irrespective of the cell type, sarcosine stimulates up-regulation of distinct sets of genes involved in cell cycle and mitosis, while down-regulates expression of genes driving apoptosis. Moreover, it was found that in all cell types, sarcosine had pronounced stimulatory effects on clonogenicity. Except of an inhibitor of histone deacetylase valproic acid, efficiency of all agents was significantly (P < 0.05) decreased in sarcosine pre-incubated cells., Conclusions: Our comparative study brings evidence that sarcosine affects not only metastatic PCa cells, but also their malignant and non-malignant counterparts and induces very similar changes in cells behavior, but via distinct cell-type specific targets., (© 2017 Wiley Periodicals, Inc.)

The interaction of a plethora nanoparticles with major biota such as plants and animals/humans has been the subject of various multidisciplinary studies with special emphasis on toxicity aspects. However, reports are meager on the transport phenomena of nanoparticles in the plant-animal/human system. Since plants and animals/humans are closely linked via food chain, discussion is imperative on the main processes and mechanisms underlying the transport phenomena of nanoparticles in the plant-animal/human system, which is the main objective of this paper. Based on the literature appraised herein, it is recommended to perform an exhaustive exploration of so far least explored aspects such as reproducibility, predictability, and compliance risks of nanoparticles, and insights into underlying mechanisms in context with their transport phenomenon in the plant-animal/human system. The outcomes of the suggested studies can provide important clues for fetching significant benefits of rapidly expanding nanotechnology to the plant-animal/human health-improvements and protection as well., (Copyright © 2016 Elsevier Inc. All rights reserved.)