Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin

For the treatment of severe COVID-19, supplementation with human plasma-purified α-1 antitrypsin (AAT) to patients is currently considered. AAT inhibits host proteases that facilitate viral entry and possesses broad anti-inflammatory and immunomodulatory activities. Researchers have demonstrated that an interaction between SARS-CoV-2 spike protein (S) and lipopolysaccharides (LPS) enhances pro-inflammatory responses in vitro and in vivo. Hence, we wanted to understand the potential anti-inflammatory activities of plasma-derived and recombinant AAT (recAAT) in a model of human total peripheral blood mononuclear cells (PBMCs) exposed to a combination of CHO expressed trimeric spike protein and LPS, ex vivo. We confirmed that cytokine production was enhanced in PBMCs within six hours when low levels of LPS were combined with purified spike proteins (“spike”). In the presence of 0.5 mg/mL recAAT, however, LPS/spike-induced TNF-α and IL-1β mRNA expression and protein release were significantly inhibited (by about 46–50%) relative to LPS/spike alone. Although without statistical significance, recAAT also reduced production of IL-6 and IL-8. Notably, under the same experimental conditions, the plasma-derived AAT preparation Respreeza (used in native and oxidized forms) did not show significant effects. Our findings imply that an early pro-inflammatory activation of human PBMCs is better controlled by the recombinant version of AAT than the human plasma-derived AAT used here. Considering the increasing clinical interest in AAT therapy as useful to ameliorate the hyper-inflammation seen during COVID-19 infection, different AAT preparations require careful evaluation.     

Copper,Iron, and Manganese Toxicity in Neuropsychiatric Conditions

Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. An imbalance in the levels of these metals weakens the structural, regulatory, and catalytic roles of different enzymes, proteins, receptors, and transporters and is known to provoke the development of various neurological conditions through different mechanisms, such as via induction of oxidative stress, increased α-synuclein aggregation and fibril formation, and stimulation of microglial cells, thus resulting in inflammation and reduced production of metalloproteins. In the present review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. In our review, we described diseases related to these metals, such as aceruloplasminaemia, neuroferritinopathy, pantothenate kinase-associated neurodegeneration (PKAN) and other very rare classical NBIA forms, manganism, attention-deficit/hyperactivity disorder (ADHD), ephedrone encephalopathy, HMNDYT1-SLC30A10 deficiency (HMNDYT1), HMNDYT2-SLC39A14 deficiency, CDG2N-SLC39A8 deficiency, hepatic encephalopathy, prion disease and “prion-like disease”, amyotrophic lateral sclerosis, Huntington’s disease, Friedreich’s ataxia, and depression.     

Heavy metal behaviour in peat - A mineralogical perspective

The mineralogical composition of a 40 cm subsurface layer of transitional mire ‘Bagno Bruch’ (southern Poland) polluted with atmospheric dust was studied using scanning electron microscopy. The mire is located 9 km to the east of a zinc smelter on the northern limit of industrial Upper Silesia in southern Poland. Concentrations of zinc, lead and cadmium reach values of 494, 238 and 16 mg kg⁻¹, respectively, in the peat layer.Inorganic particles in the peat were grouped into two main categories based on their origin: air dust particles of anthropogenic- and natural sources, and authigenic minerals that originated within the mire. Anthropogenic particles comprise an important part of the inorganic particles in the peat. As they are typically enriched in heavy metals, their stability is critical to controlling metal mobilities. Spheroidal aluminosilicate fly-ash particles are the most common- and most stable anthropogenic pollutants. Partially dissolved Pb-bearing particles (sulphides, chlorides and oxides) and ZnS occur as trace components throughout the peat profile. The prolonged existence of the particles made them susceptible to gravitational relocation in the peat and limits the biogeochemical cycling of the constituent elements. The least resistant Fe (hydro)oxides release Zn and minor amounts of Mn, Mg and Sn due to reductive dissolution. The released Zn is immobilized in the form of ZnS spherules, 1-3 μm in diameter, approximately 10 cm further down in the profile.The investigation shows that the behaviour of trace elements in polluted peatland is controlled by mineral dissolution/precipitation processes. The formation of authigenic minerals (ZnS, barite, gypsum) indicates complex redox conditions and element redistribution in the transitional mire.     

Impact of the modification method of Ni/ZrO2 catalyst by alkali and alkaline earth metals on its activity in thermo-chemical conversion of cellulose

The goal of this work is to determine an impact of the modification method of Ni/ZrO₂ catalyst by alkali and alkaline earth metals on its activity in thermo-chemical conversion of cellulose to hydrogen-rich gas. Me_xO-ZrO₂ supports (where Me = Ca, Mg, Na or K) were prepared by impregnation, precipitation and sol-gel methods. The obtained results reveal that an introduction of dopants to the zirconia support considerably enhances the H₂ yield in comparison to unmodified catalyst. An increase in the hydrogen formation is accompanied by a rise in the total volume of the produced gases. It is demonstrated that the highest amount of hydrogen is formed in the presence of the catalysts containing CaO-ZrO₂ support followed by Na doped materials. This phenomenon can be attributed to more efficient incorporation of Ca²⁺ and Na⁺ cations in the zirconia lattice making it more stable in the reaction conditions. Moreover, it is observed that an activity order of the investigated catalysts is consistent with the changes in the basic character of their surface.     

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine derivatives. The study was performed using CCRF/CEM and MCF-7 cell lines. Comet assay, polarography, inhibition of topoisomerase II activity, histone acetylation, and molecular docking studies were performed. Each tested compound displayed interaction with DNA and topoisomerase II, but did not cause histone acetylation. Compound 2 (9-methoxy-5,6-dimethyl-1-({[1-hydroxy-2-(hydroxymethyl)butan-2-yl]amino}methyl)-6H-pyrido[4,3-b]carbazole) was found to be the best candidate as an anticancer drug because it had the highest affinity for topoisomerase II and caused the least genotoxic damage in cells.     

Metabolic profiles of cow's blood; a review

The term ‘metabolic profile’ refers to the analysis of blood biochemical parameters that are useful to assess and prevent metabolic and nutritional disorders in dairy herds. In the higher standards of milk production, the priority in modern breeding is keeping dairy cows in high lactation and healthy. The proper analysis, as well as control. of their feeding and metabolic status is immensely important for the health condition of the herd. The disproportion between the genetically determined ability for milk production and the limitations in improving the energy value of the ration may be the cause of metabolic disorders. Negative energy balance has a major impact on the body's hormonal balance and organ functions and mostly appears during transition periods: from 3 to 2 weeks prepartum until 2–3 weeks postpartum. The term ‘transition’ is used to underscore the important physiological, metabolic and nutritional changes occurring in this time. The manner in which these changes occur and how they are diagnosed and detected are extremely important, as they are closely related to clinical and subclinical postpartum diseases, lactation and reproductive performance – factors that significantly shape the profitability of production. Therefore the priority for intensive milk production is prevention of metabolic diseases and other disorders. It is the intent of this review to synthesize and summarize the information currently available on metabolic status and physiological changes in the cow's body that occur during lactation, as well as to discuss the interpretation of the results, which will be a useful diagnostic tool in nutritional evaluations of the dairy herd. © 2016 Society of Chemical Industry     

Comparative Evaluation of Sucrosomial Iron and Iron Oxide Nanoparticles as Oral Supplements in Iron Deficiency Anemia in Piglets

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.