Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.

Background The Wnt/β-catenin signalling is aberrantly activated in primary B cell chronic lymphocytic leukaemia (CLL). Epigenetic silencing of pathway inhibitor genes may be a mechanism for its activation. In this study, we investigated systematically and quantitatively the methylation status of 12 Wnt/β-catenin pathway inhibitor genes – CDH1, DACT1, DKK1, DKK2, DKK3, DKK4, SFRP1, SFRP2, SFRP3, SFRP4, SFRP5 and WIF1 – in the cell lines EHEB and MEC-1 as well as patient samples. Methods Quantification of DNA methylation was performed by means of bisulphite pyrosequencing and confirmed by bisulphite Sanger sequencing. Gene expression was analysed by qPCR using GAPDH as internal control. E-cadherin and β-catenin protein quantification was carried out by microsphere-based immunoassays. Methylation differences observed between the patient and control groups were tested using generalised least squares models. Results For 10 genes, a higher methylation level was observed in tumour material. Only DKK4 exhibited similarly high methylation levels in both tumour and normal specimens, while DACT1 was always essentially unmethylated. However, also for these inhibitors, treatment of cells with the demethylating agent 5-aza-2´-deoxycytidine resulted in an induction of their expression, as shown by quantitative PCR, suggesting an indirect epigenetic control of activity. While the degree of demethylation and its transcriptional consequences differed between the genes, there was an overall high correlation of demethylation and increased activity. Protein expression studies revealed that no constitutive Wnt/β-catenin signalling occurred in the cell lines, which is in discrepancy with results from primary CLL. However, treatment with 5-aza-2´-deoxycytidine caused accumulation of β-catenin. Simultaneously, E-cadherin expression was strongly induced, leading to the formation of a complex with β-catenin and thus demonstrating its epigenetically regulated inhibition effect. Conclusions The results suggest an epigenetic silencing mechanism of the Wnt/β-catenin pathway inhibitor genes in CLL. Hypermethylation and silencing of functionally related genes may not be completely stochastic but result from the tumour epigenome reprogramming orchestrated by Polycomb-group repressive complexes. The data are of interest in the context of epigenetic-based therapy.

The beneficial properties of algae make them perfect functional ingredients for food products. Algae have a high energy value and are a source of biologically active substances, proteins, fats, carbohydrates, vitamins, and macro- and microelements. They are also rich in polyunsaturated fatty acids, proteins, mycosporine-like amino acids, polysaccharides, polyphenols, carotenoids, sterols, steroids, lectins, halogenated compounds, polyketides, alkaloids, and carrageenans. Different extraction parameters are used depending on the purpose and the substances to be isolated. In this study, the following parameters were used: hydromodule 1:10 and an extraction duration of 1–2 h at the extraction temperature of 25–40 °C. A 30–50% solution of ethanol in water was used as an extractant. Algae extracts can be considered as potential natural sources of biologically active compounds with antimicrobial activity and antiviral properties. The content of crude protein, crude fat, and carbohydrates in U. Prolifera, C. racemosa var. peltata (Chlorophyta), S. oligocystum and S. fusiforme (SF-1) was studied. It was found that C. muelleri (Bacillariophyta), I. galbana (Haptophyta), and T. weissflogii (Bacillariophyta) contain about 1.9 times more omega-3 than omega-6 fatty acids. N. gaditana (Ochrophyta), D. salina (Chlorophyta), P. tricornutum (Bacillaryophyta) and I. galbana (Haptophyta) extracts showed inhibitory activity of varying intensities against E. coli or P. aeruginosa. In addition, algae and algae-derived compounds have been proposed to offer attractive possibilities in the food industry, especially in the meat sector, to evolve functional foods with myriad functionalities. Algae can increase the biological activity of food products, while the further study of the structure of compounds found in algae can broaden their future application possibilities.

The aim of this article is to increase the nutritional value of soybean meal while reducing the content of antinutrients by microbial fermentation of soybean meal with a mixed culture of probiotic microorganisms (Bacillus subtilis, Aspergillus niger, Saccharomyces cerevisiae, Lactiplantibacillus plantarum) at two different hydromodules. The addition of microorganisms increased the content of easily digestible protein and amine nitrogen in fermented soybean meal (30:110 and 30:130, hydromodulus soybean meal:water) while decreasing urease activity (hydromodulus 30:110). The positive effect of microbial fermentation on the mineral composition of soybean meal was demonstrated. The ability of microorganisms in the fermentation process to increase the content of protein, essential amino acids, and macro- and microelements in soybean meal while decreasing anti-nutritional factors opens up possibilities for using this technology to advance animal husbandry.