Dual activity of triterpenoids: apoptotic versus antidifferentiation effects

Triterpenoids are natural, biologically active compounds extracted from many plants. They possess antiinflammatory, anticancer, and antioxidant properties. In the report presented, antiproliferative effects and leukemia cell growth and apoptosis modulating activities of ursolic acid (UA) and oleanolic acid (OA) were investigated. Both triterpenoids are inhibitors of leukemia cell growth and inductors of apoptosis. However, when applied in combination with anthracycline antitumor antibiotic doxorubicin (Dox), UA and OA diversely modulate therapeutic efficacy of Dox, due to different antioxidant activities. Compare to OA showing synergism/additive effect with Dox, UA (stronger antioxidant) acts antagonistically and reduces leukemia cell growth inhibiting and differentiation effects induced by Dox. In conclusion, these findings suggest that although triterpenoids UA and OA can induce apoptosis, their antioxidant activities can interfere with the therapeutic effect of antitumor antibiotic Dox which mechanism of action is attributed to the production of reactive oxygen species.     

Oxidative stress and electron spin resonance

The body constantly reacts with oxygen as part of the energy producing processes of cells. Oxidative stress is a dysbalance between the production of free radicals as products of these reactions and antioxidant properties of cells. The factors influencing the production of free radicals are physical agents, chemical agents and biological agents. Free radicals are paramagnetic molecules with short time-period for their detection by electron spin resonance (ESR) spectroscopy. The free radical stabilization can be gained by freezing a solution of an organic radical or bonding to spin trapping agents. The spin trapping agents are diamagnetic compounds which rapidly scavenge transient radicals to form stable paramagnetic spin adducts radicals. Because this secondary radical retains an unpaired electron, it can often be detected by electron spin resonance. From ESR spectra can be obtained structural information and kinetic information, information about the formation and decay of the radicals. To study the process of free radical generation is an important step towards reducing the deteriorating effects of oxidative stress.     

Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In-depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD-1/PD-L1&PD-L2, TIGIT/PVR, CD137/CD137-L, CTLA-4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies.     

Patterns of Diversity of Fusarium Fungi Contaminating Soybean Grains

Soybean is an important, high protein source of food and feed. However, like other agricultural grains, soybean may pose a risk to human and animal health due to contamination of the grains with toxigenic Fusaria and associated mycotoxins. In this study, we investigated the diversity of Fusaria on a panel of 104 field isolates obtained from soybean grains during the growing seasons in 2017–2020. The results of species-specific PCR analyses showed that Fusarium avenaceum was the most common (n = 40) species associated with soybean grains in Poland, followed by F. equiseti (n = 22) and F. sporotrichioides (11 isolates). A set of isolates, which was not determined based on PCR analyses, was whole genome sequenced. Multiple sequence analyses using tef-1α, top1, rpb1, rpb2, tub2, pgk, cam and lsu genes showed that most of them belonged to Equiseti clade. Three cryptic species from this clade: F. clavum, F. flagelliforme and FIESC 31 (lacking Latin binomial) were found on soybean for the first time. This is the first report demonstrating the prevalence of Fusaria on soybean grains in Poland.     

Properties of Eco-Friendly Particleboards Bonded with Lignosulfonate-Urea-Formaldehyde Adhesives and pMDI as a Crosslinker

The purpose of this study was to evaluate the feasibility of using magnesium and sodium lignosulfonates (LS) in the production of particleboards, used pure and in mixtures with urea-formaldehyde (UF) resin. Polymeric 4,4′-diphenylmethane diisocyanate (pMDI) was used as a crosslinker. In order to evaluate the effect of gradual replacement of UF by magnesium lignosulfonate (MgLS) or sodium lignosulfonate (NaLS) on the physical and mechanical properties, boards were manufactured in the laboratory with LS content varying from 0% to 100%. The effect of LS on the pH of lignosulfonate-urea-formaldehyde (LS-UF) adhesive compositions was also investigated. It was found that LS can be effectively used to adjust the pH of uncured and cured LS-UF formulations. Particleboards bonded with LS-UF adhesive formulations, comprising up to 30% LS, exhibited similar properties when compared to boards bonded with UF adhesive. The replacement of UF by both LS types substantially deteriorated the water absorption and thickness swelling of boards. In general, NaLS-UF-bonded boards had a lower formaldehyde content (FC) than MgLS-UF and UF-bonded boards as control. It was observed that in the process of manufacturing boards using LS adhesives, increasing the proportion of pMDI in the adhesive composition can significantly improve the mechanical properties of the boards. Overall, the boards fabricated using pure UF adhesives exhibited much better mechanical properties than boards bonded with LS adhesives. Markedly, the boards based on LS adhesives were characterised by a much lower FC than the UF-bonded boards. In the LS-bonded boards, the FC is lower by 91.1% and 56.9%, respectively, compared to the UF-bonded boards. The boards bonded with LS and pMDI had a close-to-zero FC and reached the super E0 emission class (≤1.5 mg/100 g) that allows for defining the laboratory-manufactured particleboards as eco-friendly composites.     

Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper

Several randomized controlled trials have shown that population‐based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high‐risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population‐based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic‐based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis.     

Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients

Invasive fungal diseases are important causes of morbidity and mortality in immunocompromised patients. Patients with haematological malignancies and solid cancers, as well as those with allogeneic haematopoietic stem cell and solid organ transplants, are at high risk of developing such an infection. Many fungi can cause invasive disease, with Aspergillus spp. and Candida spp. being the prevalent fungal pathogens infecting susceptible patients. During the past few years, rare moulds (for example Zygomycetes and Fusarium spp.) have come into focus as the cause of devastating clinical disease. This review aims to analyse environmental factors and parameters related to impairment of the immune system that are thought to favour the onset of invasive mould infections. Some moulds are quite common among all categories of patients, while others appear to be limited to a given subset of patients, such as allogeneic haematopoietic stem cell or solid organ transplant recipients. In addition to an exploration of factors that predispose patients to the acquisition of an invasive mould infection, prognostic factors that help to predict the eventual outcome of these infections are identified.