Machine learning (ML) is a broad term encompassing several methods that allow us to learn from data. These methods may permit large real-world databases to be more rapidly translated to applications to inform patient-provider decision-making. This paper presents a review of articles that discuss the use of Fourier transform infrared (FTIR) spectroscopy and ML for human blood analysis between the years 2019-2023. The literature review was conducted to identify published research of employed ML linked with FTIR for distinction between pathological and healthy human blood cells. The articles\' search strategy was implemented and studies meeting the eligibility criteria were evaluated. Relevant data related to the study design, statistical methods, and strengths and limitations were identified. A total of 39 publications in the last 5 years (2019-2023) were identified and evaluated for this review. Diverse methods, statistical packages, and approaches were used across the identified studies. The most common methods included support vector machine (SVM) and principal component analysis (PCA) approaches. Most studies applied internal validation and employed more than one algorithm, while only four studies applied one ML algorithm to the data. A wide variety of approaches, algorithms, statistical software, and validation strategies were employed in the application of ML methods. There is a need to ensure that multiple ML approaches are used, the model selection strategy is clearly defined, and both internal and external validation are necessary to be sure that the discrimination of human blood cells is being made with the highest efficient evidence.

Domoic acid (DA) is an excitatory marine neurotoxin produced by diatoms Pseudo-nitzschia spp. as a defence compound that accumulates in the food web and is associated with amnesic shellfish poisoning in humans. Although its toxicity has been well established in marine species, there is limited data on DA cytogenotoxicity in human non-target cells. Therefore, we aimed to investigate the cytogenotoxic potential of DA (0.01-10 μg/mL) in human peripheral blood cells (HPBCs) using a battery of bioassays in vitro. In addition, the influence of DA on oxidative stress parameters as a possible mechanism of action was assessed. Results revealed that DA induced dose- and time-dependent cytotoxic effects. DA significantly affected genomic instability by increasing the frequency of micronuclei and nuclear buds. Furthermore, a slight induction of primary DNA strand breaks was detected after 24 h of exposure accompanied by a significant increase in the number of abnormal size tailed nuclei. No induction of hOGG1 (human 8-oxoguanine DNA glycosylase) sensitive sites was determined upon exposure to DA. Additionally, DA induced oxidative stress by increased production of reactive oxygen species accompanied by changes in glutathione, superoxide dismutase, malondialdehyde and protein carbonyl levels. Overall, the obtained results showed adverse genotoxic effects of DA in non-target HPBCs.

The non-proteinogenic amino acid ß-N-methylamino-l-alanine (BMAA) is associated with the development of neurodegenerative diseases such as Alzheimer\'s disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC) and amyotrophic lateral sclerosis. BMAA is known to induce neurotoxic effects leading to neurodegeneration via multiple mechanisms including misfolded protein accumulation, glutamate induced excitotoxicity, calcium dyshomeostasis, endoplasmic reticulum stress and oxidative stress. In the present study, for the first time, genotoxic activity of BMAA (2.5, 5, 10 and 20 μg/mL) was studied in human peripheral blood cells (HPBCs) using the comet and cytokinesis-block micronucleus cytome assays. In addition, the influence of BMAA on the oxidative stress was assessed. At non-cytotoxic concentrations BMAA did not induce formation of DNA strand breaks in HPBCs after 4 and 24 h exposure; however, it significantly increased the number of micronuclei after 24 and 48 h at 20 μg/mL and nucleoplasmic bridges after 48 h at 20 μg/mL. The frequency of nuclear buds was slightly though non-significantly increased after 48 h. Altogether, this indicates that in HPBCs BMAA is clastogenic and induces complex genomic alterations including structural chromosomal rearrangements and gene amplification. No influence on oxidative stress markers was noticed. These findings provide new evidence that environmental neurotoxin BMAA, in addition to targeting common pathways involved in neurodegeneration, can also induce genomic instability in non-target HPBCs suggesting that it might be involved in cancer development. Therefore, these data are important in advancing our current knowledge and opening new questions in the understanding of the mechanisms of BMAA toxicity, particularly in the context of genotoxicity.

The single-wall carbon nanotubes (SWCNTs) are one of the new materials ofemerging technologies. They are becoming increasingly studied for the possibleapplications in electronics, optics and biology. In particular, very promising fields ofapplication are the development of optical biosensors and the intracellular drug delivery.Nevertheless, there is a paucity of information on their toxicological properties and onpotential human health risk. In the present study the SWCNTs were investigated for thepossible induction of toxicity in human blood cells. Cell growth, viability, apoptosis andmetabolic activity were evaluated in proliferating human peripheral blood lymphocytes. Inun-stimulated human leukocytes primary DNA damage was also evaluated. SWCNTsconcentrations ranging from 1 to 50 μg/ml were tested, and treatment duration varied from6 to 72 h, in accordance with the biological target investigated. A statistically significantdecrease in cell growth was found in cells treated with the highest concentrations (25 and50 μg/ml). Such decrease was not associated to cell death or apoptosis, but it wasdemonstrated to be related to a decrease in metabolic activity, as assessed by resazurinassay. Moreover, treatments of 6 h with SWCNTs concentrations of 1, 5 and 10 μg/mlfailed to induce primary DNA damage on the entire human leukocytes population.

Atomic force microscopy (AFM) is a useful and powerful tool to study molecular interactions applied to nanomedicine. The aim of the present study was to implement a hands-on atomic AFM course for graduated biosciences and medical students. The course comprises two distinct practical sessions, where students get in touch with the use of an atomic force microscope by performing AFM scanning images of human blood cells and force spectroscopy measurements of the fibrinogen-platelet interaction. Since the beginning of this course, in 2008, the overall rating by the students was 4.7 (out of 5), meaning a good to excellent evaluation. Students were very enthusiastic and produced high-quality AFM images and force spectroscopy data. The implementation of the hands-on AFM course was a success, giving to the students the opportunity of contact with a technique that has a wide variety of applications on the nanomedicine field. In the near future, nanomedicine will have remarkable implications in medicine regarding the definition, diagnosis, and treatment of different diseases. AFM enables students to observe single molecule interactions, enabling the understanding of molecular mechanisms of different physiological and pathological processes at the nanoscale level. Therefore, the introduction of nanomedicine courses in bioscience and medical school curricula is essential.

Na(+)/K(+)-ATPase is in charge of maintaining the ionic and osmotic intracellular balance by using ATP as an energy source to drive excess Na(+) ions out of the cell in exchange for K(+) ions. We explored whether three representative cytotoxic gold(III) compounds might interfere with Na(+)/K(+)-ATPase and cause its inhibition at pharmacologically relevant concentrations. The tested complexes were [Au(bipy)(OH)2][PF6] (bipy=2,2\'-bipyridine), [Au(py(dmb)-H)(CH3COO)2] (py(dmb)-H=deprotonated 6-(1,1-dimethylbenzyl)-pyridine), and [Au(bipy(dmb)-H)(OH)][PF6] (bipy(dmb)-H=deprotonated 6-(1,1-dimethylbenzyl)-2,2\'-bipyridine). We found that all of them caused a pronounced and similar inhibition of Na(+)/K(+)-ATPase activity. Inhibition was found to be non-competitive and reversible. Remarkably, treatment with cysteine resulted in reversal or prevention of Na(+)/K(+)-ATPase inhibition. It is very likely that the described effects may contribute to the overall cytotoxic profile of these gold complexes.

Iron oxide nanoparticles (ION) can have a wide scope of applications in biomedicine, namely in magnetic resonance imaging, tissue repair, drug delivery, hyperthermia, transfection, tissue soldering, and as antimicrobial agents. The safety of these nanoparticles, however, is not completely established, namely concerning their effect on immune system and inflammatory pathways. The aim of this study was to evaluate the in vitro effect of polyacrylic acid (PAA)-coated ION and non-coated ION on the production of six cytokines [interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma (IFN-γ) and interleukin 10 (IL-10)] by human peripheral blood cells, and to determine the inflammatory pathways involved in this production. The obtained results showed that PAA-coated and non-coated ION were able to induce all the tested cytokines and that activation of transforming growth factor beta (TGF-β)-activated kinase (TAK1), p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun N-terminal kinases (JNK) were involved in this effect.