Comparison of Antiplatelet Effects of Phenol Derivatives in Humans

Flavonoids are associated with positive cardiovascular effects. However, due to their low bioavailability, metabolites are likely responsible for these properties. Recently, one of these metabolites, 4-methylcatechol, was described to be a very potent antiplatelet compound. This study aimed to compare its activity with its 22 close derivatives both of natural or synthetic origin in order to elucidate a potential structure–antiplatelet activity relationship. Blood from human volunteers was induced to aggregate by arachidonic acid (AA), collagen or thrombin, and plasma coagulation was also studied. Potential toxicity was tested on human erythrocytes as well as on a cancer cell line. Our results indicated that 17 out of the 22 compounds were very active at a concentration of 40 μM and, importantly, seven of them had an IC50 on AA-triggered aggregation below 3 μM. The effects of the most active compounds were confirmed on collagen-triggered aggregation too. None of the tested compounds was toxic toward erythrocytes at 50 μM and four compounds partly inhibited proliferation of breast cancer cell line at 100 μM but not at 10 μM. Additionally, none of the compounds had a significant effect on blood coagulation or thrombin-triggered aggregation. This study hence reports four phenol derivatives (4-ethylcatechol, 4-fluorocatechol, 2-methoxy-4-ethylphenol and 3-methylcatechol) suitable for future in vivo testing.

Morphological, Gene, and Hormonal Changes in Gonads and In-Creased Micrococcal Nuclease Accessibility of Sperm Chromatin Induced by Mercury

Mercury is one of the most dangerous environmental pollutants. In this work, we analysed the effects of exposure of Mytilus galloprovincialis to 1, 10 and 100 pM HgCl2 for 24 h on the gonadal morphology and on the expression level of three stress genes: mt10, hsp70 and πgst. In this tissue we also evaluated the level of steroidogenic enzymes 3β-HSD and 17β-HSD and the expression of PL protein genes. Finally, we determined difference in sperm chromatin accessibility to micrococcal nuclease. We found alterations in gonadal morphology especially after exposure to 10 and 100 pM HgCl2 and hypo-expression of the three stress genes, particularly for hsp70. Furthermore, decreased labelling with both 3β-HSD and 17β-HSD antibodies was observed following exposure to 1 and 10 pM HgCl2 and complete absence at 100 pM HgCl2 exposure. Gonads of mussels exposed to all HgCl2 doses showed decreased expression of PL protein genes especially for PLIII. Finally, micrococcal nuclease digestions showed that all doses of HgCl2 exposure resulted in increased sperm chromatin accessibility to this enzyme, indicative of improper sperm chromatin structure. All of these changes provide preliminary data of the potential toxicity of mercury on the reproductive health of this mussel.

Sunitinib-Induced Adrenal Crisis in a Patient with Pre-Existing Immunotherapy-Related Hypopituitarism

Sunitinib is a tyrosine kinase inhibitor that is frequently used in the treatment of metastatic renal cell carcinoma (mRCC). As a multikinase inhibitor, numerous off-target side effects of this medication are widely recognized. More recently, endocrine side effects, including hypoadrenalism, are becoming more apparent. We report a case in which a 71-year-old female experienced recurrent adrenal crises when managed with sunitinib for mRCC on a background of immune-related hypopituitarism and hypoadrenalism as a result of previous treatment with immunotherapy. Clinicians should be aware of this potential toxicity when using such medications and consider further investigation in the appropriate clinical setting.

Intracellular copper storage and delivery in a bacterium

A family of cytosolic copper (Cu) storage proteins (the Csps) are widespread in bacteria. The Csps can bind large quantities of Cu(I) via their Cys-lined four-helix bundles, and the majority are cytosolic (Csp3s). This is inconsistent with the current dogma that bacteria, unlike eukaryotes, have evolved not to maintain intracellular pools of Cu due to its potential toxicity. Sporulation in Bacillus subtilis has been used to investigate if a Csp3 can store Cu(I) in the cytosol for a target enzyme. The activity of the Cu-requiring endospore multi-Cu oxidase BsCotA (a laccase) increases under Cu-replete conditions in wild type B. subtilis, but not in the strain lacking BsCsp3. Cuprous ions readily transfer from BsCsp3, but not from the cytosolic copper metallochaperone BsCopZ, to BsCotA in vitro producing active enzyme. Both BsCsp3 and BsCotA are upregulated during late sporulation. The hypothesis we propose is that BsCsp3 acquires and stores Cu(I) in the cytosol for BsCotA.

Soil and Leaf Mineral Element Contents in Mediterranean Vineyards: Bioaccumulation and Potential Soil Pollution

The study reported here concerns the geochemical distributions of macro- and trace elements (including potentially toxic elements, PTEs) in the vineyard soils of Alcubillas, which is one of the oldest, albeit not world-renowned, wine-growing areas in La Mancha (Central Spain). Soil and leaf samples were analyzed by X-ray fluorescence spectrometry to ascertain the levels of various elements in the soil and the plant. The potential toxicity of the elements was assessed with regard to the development of the vineyard. Despite the fact that fertilizers and pesticides are employed in the vineyards in this area, the results showed that the levels of trace elements in the soil samples did not exceed the reference values according the pedogeochemical values for the region and Spain. This finding suggests that the study area is not polluted, and therefore, there are hardly any traces of anthropogenic contamination. The Biological Absorption Coefficient (BAC) was calculated to assess the assimilation of various elements from the soil to the leaves, and differences were found in the element absorption capacity of the vines. Some elements were not taken up by Vitis vinifera despite elements like Zr and Rb being present in relatively high concentrations in the soil. The production in these soils does not represent a threat to human health or the ecosystem, because the farmers in this area are extremely careful to preserve the environment and they only farm to achieve moderate yields of grapes per hectare.

Assessment of Potential Toxicity of Onion-like Carbon Nanoparticles from Grilled Turbot Scophthalmus maximus L.

Although the presence of foodborne nanoparticles was confirmed in grilled fish in a previous study, the evaluation of potential health risks of these NPs was insufficient. In the present study, the potential toxicity of onion-like carbon nanoparticles (OCNPs) separated from grilled turbot Scophthalmus maximus L. was evaluated using mouse osteoblasts cells model and zebrafish (Danio rerio) model. Cytotoxicity evaluation revealed that the OCNPs penetrated into the MC3T3-E1 cells without arousing cell morphology changes. No evident apoptosis or damage of cells was observed with increasing OCNPs’ concentration to 20 mg/mL. In the hemolysis test, OCNPs did not show an obvious hemolysis effect on red blood cells. In the acute toxicity test, the LC50 value (212.431 mg/L) of OCNPs to zebrafish showed a weak acute toxicity. In subacute toxicity test, after exposure to OCNPs (30 mg/L, 40 mg/L) for 10 days, a significant increase of reactive oxygen species level of zebrafish was observed. Meanwhile, redundant ROS content caused inhibition to several antioxidant enzymes and induced lipid and protein peroxidation damages according to the upregulation of malondialdehyde and protein carbonyl levels. The chronic toxicity test results indicated that oxidative stress was only observed in the high concentration group of OCNPs-treated zebrafish.

An Up-to-Date Review of Natural Nanoparticles for Cancer Management

Cancer represents one of the leading causes of morbidity and mortality worldwide, imposing an urgent need to develop more efficient treatment alternatives. In this respect, much attention has been drawn from conventional cancer treatments to more modern approaches, such as the use of nanotechnology. Extensive research has been done for designing innovative nanoparticles able to specifically target tumor cells and ensure the controlled release of anticancer agents. To avoid the potential toxicity of synthetic materials, natural nanoparticles started to attract increasing scientific interest. In this context, this paper aims to review the most important natural nanoparticles used as active ingredients (e.g., polyphenols, polysaccharides, proteins, and sterol-like compounds) or as carriers (e.g., proteins, polysaccharides, viral nanoparticles, and exosomes) of various anticancer moieties, focusing on their recent applications in treating diverse malignancies.

Investigations on the Accumulation, Tissue Distribution and Toxicity of Silver Nanoparticles in Amammalian Model

The current work aimed to investigate the potential toxicity of Ag-NPs in male rabbits as a mammalian model, following acute and sub-acute dermal exposure terms. The rabbits were topically exposed to a single acute dose of 2.0% Ag-NPs and the assessments were conducted4 days latter, while a dose of 0.5% was administered every other day for the sub-acute exposure in two time periods (7 and 14 days). The accumulation and retention of Ag+ ions in the skin and their distribution in other vital tissues were measured. In addition, the concentrations of total proteins, lipidparameters and levels of different oxidative stress biomarkers in the skin were also evaluated. The results demonstrated the ability of Ag-NPs to penetrate the skin and accumulate rapidly in the dermal skin, then spread out to the blood and other vital organs. The spleen and liver seemed to be the main target organs. The high levels of Ag+ tissue accumulation affected the concentration of total proteins and acted as a stressor stimulus within the skin, thereby, initiating oxidative stress. The liberated ROS caused disruption of the activities of the antioxidant enzymes GST, GSH, GR, GPx, SOD and CAT as well as increased levels of H2O2 and MDA. The current work showed that the toxicity of Ag-NPs could be attributed to the release of Ag+ ions and the subsequent excessive generation of ROS.