Heme Oxygenase Modulation Drives Ferroptosis in TNBC Cells

The term ferroptosis refers to a peculiar type of programmed cell death (PCD) mainly characterized by extensive iron-dependent lipid peroxidation. Recently, ferroptosis has been suggested as a potential new strategy for the treatment of several cancers, including breast cancer (BC). In particular, among the BC subtypes, triple negative breast cancer (TNBC) is considered the most aggressive, and conventional drugs fail to provide long-term efficacy. In this context, our study’s purpose was to investigate the mechanism of ferroptosis in breast cancer cell lines and reveal the significance of heme oxygenase (HO) modulation in the process, providing new biochemical approaches. HO’s effect on BC was evaluated by MTT tests, gene silencing, Western blot analysis, and measurement of reactive oxygen species (ROS), glutathione (GSH) and lipid hydroperoxide (LOOH) levels. In order to assess HO’s implication, different approaches were exploited, using two distinct HO-1 inducers (hemin and curcumin), a well-known HO inhibitor (SnMP) and a selective HO-2 inhibitor. The data obtained showed HO’s contribution to the onset of ferroptosis; in particular, HO-1 induction seemed to accelerate the process. Moreover, our results suggest a potential role of HO-2 in erastin-induced ferroptosis. In view of the above, HO modulation in ferroptosis can offer a novel approach for breast cancer treatment.     

Restoration of Immune Responsiveness to Glioma by Vaccination of Mice with Established Brain Gliomas with a Semi-Allogeneic Vaccine

Prior studies had shown the clinical efficacy of a semi-allogeneic glioma vaccine in mice with lethal GL261 gliomas. This was confirmed in the present study. As subcutaneous vaccination resulted in protection against tumor in the brain, the present study assessed the impact of this vaccination of mice bearing established GL261 brain gliomas on their cytokine production upon in vitro exposure to tumor-derived products. Mice with established GL261 brain gliomas were vaccinated subcutaneously with H-2^b GL261 glioma cells fused with H-2^d RAG-neo cells or with a mock vaccine of phosphate-buffered saline. The results of these analyses show that the presence of GL261 tumor-conditioned medium resulted in increased production of Th1, inflammatory and inhibitory cytokines by spleen cells from control mice and from vaccinated glioma-bearing mice. In contrast, spleen cells of tumor-bearing, mock-vaccinated mice produced lower levels of cytokines in the presence of tumor-conditioned media. However, these results also show that there was not a heightened level of cytokine production in the presence of tumor-conditioned medium by spleen cells of vaccinated mice over the production by spleen cells of control mice. Overall, these results show that vaccination slows growth of the GL261 tumors to the point where GL261-vaccinated mice do not show the signs of morbidly or splenic dysfunction exhibited by unvaccinated, late stage glioma-bearing mice.     

Distribution of arsenic compounds in Mytilus galloprovincialis of the Venice lagoon (Italy)

Samples of Mytilus galloprovincialis collected in different sites of the Venice lagoon (Italy) were investigated for total arsenic concentrations by ICP-AES and for single arsenic species by HPLC-ICP-MS. For this purpose, an analytical procedure for the sensitive and efficient speciation of the arsenic species As(III), As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AB), arsenocholine (AC), and four arsenosugars was optimised. The total arsenic and the single arsenic species were determined in both the hepatopancreas (digestive gland) and the remaining soft tissues in order to verify the different arsenic accumulation in the body parts of mussels. Arsenic compounds were extracted from the mussels with a methanol/water mixture; the extracts were evaporated to dryness, redissolved in water, and chromatographed in an anion-exchange column, a Hamilton PRP-X100. Only small quantities or traces of inorganic arsenic were detected in the mussels. The majority of arsenic compounds detected in the extracts were organic species, with a predominance of arsenobetaine and of an arsenosugar. In addition, a greater arsenic accumulation in the digestive glands of mussels was observed.     

Liquid chromatographic-mass spectrometric analysis of conjugated diene fatty acids in a partially hydrogenated fat

A commercially available partially hydrogenated fat was analyzed for fatty acids containing conjugated dienes. The fatty acids were isolated by high-performance liquid chromatography (HPLC), and analyzed with a photodiode array detector and an atmospheric-pressure ionization mass spectrometer. Conventional and second-derivative ultraviolet (UV) spectra of the peaks eluting from the HPLC were recorded with the photodiode array detector, and peaks displaying second-derivative UV spectra characteristic of the conjugated diene chromophore were analyzed by mass spectrometry. The UV and mass spectra of the fatty acids with conjugated dienes, present in the partially hydrogenated fat, were identical to those of reference preparations of linoleic acid isomers with conjugated dienes. The results obtained emphasize that care must be exercised in the interpretation of clinical and experimental data concerning the detection of conjugated dienes in tissues or body fluids of humans and experimental animals. The conjugated dienes may not reflect an ongoing process of lipid peroxidation, but may be of dietary origin.     

A Rational Revisiting of Niobium Oxophosphate Catalysts for Carbohydrate Biomass Reactions

Niobium oxophosphate acid catalyst (NbP) has great success in aqueous heterogeneous catalysis, in particular for carbohydrate biomass valorization, thanks to the water-tolerant acid properties of the LA (Lewis) and BA (Brønsted) sites. Attempts to tailor the acid properties of NbP by chemical treatment or dilution in inert matrix to disperse active NbP phase have been recently proposed in the literature (Carniti et al., Appl Catal B 193:93–102, 2016; Aronne et al., J Phys Chem C 121:17378–17389, 2017). The obtained samples have been used with success in the hydrolysis reaction of inulin to fructose and in hydrolysis plus dehydration of cellobiose to HMF. The samples have been further studied with calorimetric acid-titration measurements using 2-phenylethylamine (PEA) basic probe in various liquids (cyclohexane, water, isopropanol, and water-isopropanol mixtures) to study their intrinsic and effective acid strength. A rational revisiting of the surface acid properties of NbP and modified samples, that wants to take into account the acid-sites density and strength and the LAS to BAS ratios measured under different liquid environments in relation with their catalytic activity, is presented.     

Influence of vehicle on historical pigments colour

The colour of a paint layer is determined by the pigments mixed with a vehicle and painted on a support. According to their chemical nature, the vehicles are substances that, after drying or hardening, produce an uniform and homogeneous layer. With the aim of quantifying the influence of the medium on the specification of the painting colour, we realized samples of paintings. We considered pigments and dyes of the artist's hues using the vehicles typical of ancient times: oils (especially linseed and poppy oils), casein and egg yolk, mixed according to old recipes. Measurements were performed by reflectance spectrophotometry observing the Spectral Reflectance Factor (%SRF) trend and calculating colour changes. The colorimetric study was carried out in the CIELAB colour space related to the CIE 1964 standard observer and with the D65 illuminant. The results were evaluated also on the basis of the distribution of pigment particles on paint layers observed by scanning electron microscopy.     

Ultra high temperature high-entropy borides: Effect of graphite addition on oxides removal and densification behaviour

The introduction of 0.5–1.0 wt.% graphite to the powders prepared by Self-propagating High-temperature Synthesis (SHS) is found to be highly beneficial for the removal of oxide impurities (from 2.7-8.8 wt.% to 0.2–0.5 wt.%) during spark plasma sintering (1950°C/20 min, 20 MPa) of (Hf_0.2Mo_0.2Ta_0.2Nb_0.2Ti_0.2)B₂ and (Hf_0.2Mo_0.2Ta_0.2Zr_0.2Ti_0.2)B₂ ceramics. Concurrently, the consolidation level achieved is enhanced from about 92.5% and 88%, respectively, to values exceeding 97%. While a further increase of graphite slightly improves samples densification, final products become progressively richer of the unreacted carbon.It is assumed that graphite plays a double role during SPS, e.g. not only as a reactant during the carbothermal reduction of oxides contaminant, but also as lubricating agent for the powder particles. The latter phenomenon is likely the main responsible for the densification improvement when 3 wt.% or larger amounts of additive are used. Another positive effect is the crystallite size refinement of the high-entropy phases with the progressive abatement of oxides, to confirm that their presence promotes grain coarsening during the sintering process.     

Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bone marrow. In patients affected by multiple myeloma, vitamin D deficiency is commonly correlated with an advanced stage of the disease, greater risk of progression, the development of pathological fractures, and a worse prognosis. Changes in the vitamin D receptor often contribute to the occurrence and progress of deficiencies, which can be overcome by supplementation with vitamin D or analogues. However, in spite of the findings available in the literature, there is no clear standard of care and clinical practice varies. Further research is needed to better understand how vitamin D influences outcomes in patients with monoclonal gammopathies.