In the past decades the increased use of chromium (Cr) in several anthropogenic activities and consequent contamination of soil and water have become an increasing concern. Cr exists in several oxidation states but the most stable and common forms are Cr(0), Cr(III) and Cr(VI) species. Cr toxicity in plants depends on its valence state. Cr(VI) as being highly mobile is toxic, while Cr(III) as less mobile is less toxic. Cr is taken up by plants through carriers of essential ions such as sulphate. Cr uptake, translocation, and accumulation depend on its speciation, which also conditions its toxicity to plants. Symptoms of Cr toxicity in plants are diverse and include decrease of seed germination, reduction of growth, decrease of yield, inhibition of enzymatic activities, impairment of photosynthesis, nutrient and oxidative imbalances, and mutagenesis.

The unique photoluminescent properties of upconversion nanoparticles (UCNPs) have attracted worldwide research interest and inspired many bioanalytical applications. The anti‐Stokes emission with long luminescence lifetimes, narrow and multiple absorption and emission bands, and excellent photostability enable background‐free and multiplexed detection in deep tissues. So far, however, in vitro and in vivo applications of UCNPs are restricted to the laboratory use due to safety concerns. Possible harmful effects may originate from the chemical composition but also from the small size of UCNPs. Potential end users must rely on well‐founded safety data. Thus, a risk to benefit assessment of the envisioned combined therapeutic and diagnostic (“theranostic”) applications is fundamentally important to bridge the translational gap between laboratory and clinics. The COST Action CM1403 “The European Upconversion Network—From the Design of Photon‐Upconverting Nanomaterials to Biomedical Applications” integrates research on UCNPs ranging from fundamental materials synthesis and research, detection instrumentation, biofunctionalization, and bioassay development to toxicity testing. Such an interdisciplinary approach is necessary for a better and safer theranostic use of UCNPs. Here, the status of nanotoxicity research on UCNPs is compared to other nanomaterials, and routes for the translation of UCNPs into clinical applications are delineated.

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The widespread use of silver nanoparticles (AgNPs) is accompanied by a growing concern regarding their potential risks to human health, thus calling for an increased understanding of their biological effects. The aim of this work was to systematically study the extent to which changes in cellular metabolism were dependent on the properties of AgNPs, using NMR metabolomics. Human skin keratinocytes (HaCaT cells) were exposed to citrate-coated AgNPs of 10, 30 or 60 nm diameter and to 30 nm AgNPs coated either with citrate (CIT), polyethylene glycol (PEG) or bovine serum albumin (BSA), to assess the influence of NP size and surface chemistry. Overall, CIT-coated 60 nm and PEG-coated 30 nm AgNPs had the least impact on cell viability and metabolism. The role of ionic silver and reactive oxygen species (ROS)-mediated effects was also studied, in comparison to CIT-coated 30 nm particles. At concentrations causing an equivalent decrease in cell viability, Ag(+ )ions produced a change in the metabolic profile that was remarkably similar to that seen for AgNPs, the main difference being the lesser impact on the Krebs cycle and energy metabolism. Finally, this study newly reported that while down-regulated glycolysis and disruption of energy production were common to AgNPs and H2O2, the impact on some metabolic pathways (GSH synthesis, glutaminolysis and the Krebs cycle) was independent of ROS-mediated mechanisms. In conclusion, this study shows the ability of NMR metabolomics to define subtle biochemical changes induced by AgNPs and demonstrates the potential of this approach for rapid, untargeted screening of pre-clinical toxicity of nanomaterials in general.

Excessive exposure to ultraviolet (UV) radiation is the main risk factor to develop skin pathologies or cancer because it encourages oxidative condition and skin inflammation. In this sense, strategies for its prevention are currently being evaluated. Natural products such as carotenoids or polyphenols, which are abundant in the marine environment, have been used in the prevention of oxidative stress due to their demonstrated antioxidant activities. Nevertheless, the anti-inflammatory activity and its implication in photo-prevention have not been extensively studied. Thus, we aimed to evaluate the combination of fucoxanthin (FX) and rosmarinic acid (RA) on cell viability, apoptosis induction, inflammasome regulation, and anti-oxidative response activation in UVB-irradiated HaCaT keratinocytes. We demonstrated for the first time that the combination of FX and RA (5 µM RA plus 5 μM FX, designated as M2) improved antioxidant and anti-inflammatory profiles in comparison to compounds assayed individually, by reducing UVB-induced apoptosis and the consequent ROS production. Furthermore, the M2 combination modulated the inflammatory response through down-regulation of inflammasome components such as NLRP3, ASC, and Caspase-1, and the interleukin (IL)-1β production. In addition, Nrf2 and HO-1 antioxidant genes expression increased in UVB-exposed HaCaT cells pre-treated with M2. These results suggest that this combination of natural products exerts photo-protective effects by down-regulating NRLP3-inflammasome and increasing Nrf2 signalling pathway.

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A metabolomics study of PdSpermine(Spm) on osteosarcoma MG-63 and osteoblastic HOb cells is presented to assess the impact of the potential palladium drug on cell metabolism compared with cisplatin (cDDP). Despite its higher cytotoxicity, PdSpm induced lower (and reversible) metabolic impact on MG-63 cells and the absence of apoptosis; conversely, it induced significant deviations in osteoblastic amino acid metabolism. However, when in combination with doxorubicin and methotrexate, PdSpm induced strong metabolic deviations on lipids, choline compounds, amino acids, nucleotides, and compounds related to antioxidative mechanisms (e.g., glutathione, inositol, hypoxanthine), similarly to the cDDP cocktail. Synergetic effects included triggering of lipid biosynthesis by PdSpm in the presence of doxorubicin (and reinforced by methotrexate) and changes in the glycosylation substrate uridine diphosphate acetylgalactosamine and methionine and serine metabolisms. This work provides promising results related to the impact of PdSpm on osteosarcoma cellular metabolism, particularly in drug combination protocols. Lipid metabolism, glycosylation, and amino acid metabolisms emerge as relevant features for targeted studies to further understand a potential anticancer mechanism of combined PdSpm.

Kidney ailments, as chronic kidney disease, kidney stones and polycystic kidney disease, recognized as a comorbidity of diabetes and hypertension, are strongly linked to higher risk of cardiovascular diseases, infection and cancer. Therefore, they are considered a global public health problem, contributing to the global major burden of noncommunicable diseases, and having a direct impact on high global mortality and morbidity. [1,2] It is estimated that the prevalence and associated burden of kidney disease is responsible for 5-10 million deaths per year worldwide. [2] The quantification of biomarkers present in various body fluids represents a versatile tool for diagnosis, prognosis, monitoring, therapy and disease management. [3] Currently, the most common body fluids used for biomarkers detection are blood, urine and saliva. [3] However, interstitial skin fluid (ISF), which is formed by blood transcapillary filtration is gaining increasing relevance in this realm. [4] Surrounding the capillary beds in the connective tissue, the ISF contains systemic biomarkers and its composition varies along Urea, the main nitrogenous waste product of protein metabolism, is eliminated almost exclusively by the kidney, and hence, displays considerable clinical significance in the assessment of kidney disorders. The aim of this study is to prepare and investigate the potential of swellable cross-linked gelatin methacryloyl (c-GelMA) microneedles (MNs) as a platform for minimally invasive extraction of interstitial skin fluid (ISF) toward straightforward point-of-care healthcare monitoring of renal complaints, by quantification of urea. c-GelMA MNs are successfully prepared by photo-cross-linking and micromolding, faithfully replicating the master molds (387 ± 16 µm height, 200 µm base and 500 µm tip-to-tip distance). These MN patches display good mechanical properties, withstanding more than 0.15 N per needle without breaking. Ex vivo skin insertion assays reveal that the MNs penetrate up to 237 µm depth, reaching the dermis, where they should extract ISF considering a real application. In an in vitro application using an agarose skin model system, the c-GelMA MNs are able to efficiently recover urea (>98%). Additionally, these MNs exhibit noncytotoxic effects toward human keratinocytes. These findings suggest that c-GelMA MNs are promising devices for sampling ISF and offline analysis of urea, opening new avenues for simple point-of-care healthcare monitoring.