Cellulose-containing waste recycling using fungi

Accumulation of plant waste is a serious environmental problem. Mushrooms with high cellulolytic activity can process it into valuable products that will be useful in solving various industries and agriculture problems. The enzymes of the cellulolytic complex include 1,4-β-D-glucan-4-glucanohydrolase, exo-1,4-β-glucosidase, cellobiohydrolase, β-glucosidase. 1,4-β-D-glucan-4-glucanohydrolases destroy β-1,4-glycosidic bonds within the chain of cellulose and lichenin polysaccharides. Exoglucanases destroy β-1,3- and β-1,4-glycosidic bonds at the end of the molecule. Cellobiohydrolases cleave β-1,4-glycosidic bonds to form cellobiose and glucose. β-glucosidase complete the process of destruction. Fungi with high cellulolytic activity include both representatives of the Ascomycota and Basidiomycota divisions. Ascomycete Chaetomium globosum produces endoglucanases of two families and 8 cellobiohydrolases. Myceliophthora thermophila also produces endoglucanases and cellobiohydrolases, the most abundant of which is Mt Cel7A. The fungus is a promising producer of thermostable enzymes. Trichoderma reesei has a long history of safe use as a source of highly active cellulolytic enzymes and other valuable metabolites. LPMOs of the cellulolytic fungus Thielavia terrestris are considered auxiliary enzymes, but can negatively affect the main enzymes of the complex. Irpex lacteus also produces LPMO and a complete cellulolytic enzyme complex. The cellulolytic activity of fungi and their ability to grow on cheap substrates can be used to bioconvert plant waste into valuable products. One of the ways to utilize them is to convert into compound feed with a high protein content through the use of starter cultures. The use of mushrooms will increase the content of protein and simple carbohydrates, enrich the feed with fats. Another method is to obtain cellulases, which are widely used in many industries. Thanks to the production of biodiesel and bioethanol from cellulose-containing raw materials it is possible to solve the problem of lack of fuel by replacing energy carriers from non-renewable energy sources with their environmentally friendly counterparts. They are less toxic than diesel and gasoline and are also made from renewable resources

The rs11385942 and rs657152 variants are not associated with COVID-19 severity and outcomes in patients treated with favipiravir and remdesivir

Background. There is a mounting evidence in the scientific literature that susceptibility to SARS-CoV-2 infection could vary. The severity of COVID-19 symptoms can  range from asymptomatic to severe respiratory failure, requiring prolonged artificial ventilation. The underlying causes of this range of clinical manifestations remain unclear. Identification of the risk factors that may cause this variation in clinical symptoms is important for identifying the most susceptible populations at highest risk. This should help improve prevention measures, reduce hospitalizations, and decrease the mortality rate of the disease. Previously, an association has been found between the severity of COVID-19 and the genetic markers rs11385942 G>GA and rs657152 A>C.The aim. To assess the impact of carrying polymorphic markers rs11385942 G>GA and rs657152 A>C on the severity of COVID-19 in patients undergoing specific therapy. Materials and methods. A total of 240 patients hospitalized with a coronavirus infection were included in the study. All patients received therapy with favipiravir or remdesivir. The presence of the rs11385942 G>GA and rs657152 A>C variants was determined in all patients. The study compared the length of hospital stays, frequency of patient transfers to the intensive care unit (ICU), and frequency of clinical outcomes (recovery or death) among carriers of allelic variants of the markers under investigation.Results. There were no significant associations between the carriage of variants rs11385942 G>GA and rs657152 A>C and the duration of patients’ hospitalization, frequency of patient transfers to the ICU, and patient outcomes.Conclusion. The carriage of rs11385942 G>GA and rs657152 A>C variants did not affect the severity or type of clinical outcomes in patients with COVID-19

Pharmacogenetics and pharmacokinetics of rivaroxaban in patients with atrial fibrillation and chronic kidney disease

Aim. To study the possible relationship between polymorphic variants of ABCB1 (rs2032582, rs1045642, rs1128503), CYP3A5 (rs776746), CYP3A4 (rs35599367) and CYP2J2 (rs890293) genes with residual equilibrium concentrations (Cmin,ss) of rivaroxaban in patients with non-valvular atrial fibrillation (AF) and stage 3 and 4 chronic kidney disease (CKD).Material and methods. A total of 123 patients 52 to 97 years old (median age, 82 years) with AF in combination with stage 3 and 4 CKD were included in the study. Each patient underwent a pharmacogenetic and pharmacokinetic study.Results. Cmin,ss and dose-adjusted concentration (Cmin,ss/D) of rivaroxaban were significantly higher in patients with the TT genotype than with the CT genotype of the polymorphic variant rs1045642 of the ABCB1 gene (Сmin,ss 60,5 [36,7;173] ng/ml and 54,8 [23,1;97,3] ng/ml, respectively, р=0,016; Сmin,ss/D 4,06[2,3;8,1] ng/ml/mg and 2,2 [1,1;4,9] ng/ml/mg, р=0,006). In patients with the T allele (CT and TT genotypes), compared with CC genotype carriers, Cmin,ss and Cmin,ss/D were significantly higher (Cmin,ss 60,5 [36,7;173] ng/ml and 45,8 [20,9;82,3] ng/ml, respectively, p=0,029; Cmin,ss/D 4,06 [2,3;8,1] ng/ml/  mg and 2,6 [1,2;4,8] ng/ml/mg, respectively, p=0,014). Also, Cmin,ss and Cmin,ss/D was significantly higher in patients with the TT genotype according to the polymorphic variant rs2032582 of the ABCB1 gene than in patients with the GG genotype (p=0,02 and р=0,016 respectively). Cmin,ss and Cmin,ss/D in T allele (GT and TT genotypes) carriers were significantly higher than in T allele homozygotes (Cmin,ss 57,1 [27,7;106,0] ng/ml versus 37,6 [18,6;61,7] ng/ml respectively, p=0,024; Cmin,ss/D 3,6 [1,7;7,4] ng/ml/mg versus 2,3 [1,1;4,09] ng/ml/mg respectively, p=0,032). Differences in Сmin,ss and Сmin,ss/D of rivaroxaban were detected when comparing TC, CC and TT genotypes of polymorphism rs1128503 of the ABCB1 gene. When comparing Сmin,ss and Сmin,ss/D of rivaroxaban among carriers of AG and GG genotypes of the rs776746 polymorphism of the CYP3A56986A>G gene, no significance was detected (p>0,05). Also, no difference in Cmin,ss and Cmin,ss/D was found when comparing carriers of the CC and CT genotypes of the rs35599367 polymorphism of the CYP3A4 gene, and carriers of the CC and AC genotypes of the rs890293 polymorphism of the CYP2J2 gene (p>0,05).Conclusion. The carriage of T allele by polymorphic variants rs1045642 and rs2032582 of the ABCB1 gene affects Cmin,ss and Cmin,ss/D of rivaroxaban

Effect of CYP3A4/5, ABCB1 gene polymorphisms on the residual equilibrium concentration of apixaban and bleeding in patients with non-valvular atrial fibrillation and deep vein thrombosis

Aim. The aim of our study was to investigate the influence of polymorphic markers of CYP3A4*22 CYP3A4*22 (c.522-191C>T, rs35599367), CYP3A5*3 (c.219237A>G, rs776746), ABCB1 rs1045642 (c.3435T>C) and rs4148738 (c.2692-2236C>T) genes on the plasma concentration of apixaban, on changes in prothrombin time (PT), activated partial thromboplastin time (APTT), and bleeding development in patients taking apixaban.Material and methods. The study included 108 patients with non-valvular atrial fibrillation and deep vein thrombosis receiving apixaban in therapeutic doses. Genotyping was performed by real-time polymerase chain reaction. Apixaban concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode. Because the daily dose of apixaban was different (5, 10, and 20 mg daily), the residual equilibrium concentration (Cmin,ss) of apixaban was adjusted relative to the daily drug dose (Cmin,ss/D). PT and APTT were determined using an automatic coagulometer analyzer Destiny Max (Tcoag, Ireland). Statistical processing was performed in SPSS Statistics 20.0 program.Results. We found that patients with CT ABCB1 (rs4148738) C>T genotype had higher Cmin,ss /D value than patients with TT genotype (6.23 [4;13] vs 5.77 [4;17], p=0.018). No statistically significant associations were found between carriage of CYP3A4*22 (rs35599367) C>T, CYP3A5*3 A>G, ABCB1 (rs1045642) C>T gene polymorphisms and Cmin,ss /D value of apixaban. Also, there was no significant effect of carrying polymorphisms rs35599367, rs776746, rs4148738,rs4148642, and the above genes on the risks of hemorrhagic complications. However, the influence of ABCB1 (rs1045642) C>T polymorphism on the PT value was found (TT ABCB1 (rs1045642) C>T genotype carriers the CT value wassignificantly higher than in CT genotype (17.0 [40;112] vs. 14.9 [35;132]) p=0.044).Conclusion. It was found that the Cmin,ss /D value was higher in patients with CT ABCB1 (rs4148738) C>T genotype than in patients with TT genotype. At the same time, carriage of polymorphisms of CYP3A4*22 (rs35599367) C>T, CYP3A5*3 A>G, ABCB1 (rs1045642) C>T genes did not affect the pharmacokinetics of apixaban and the risk of bleeding. We also identified the effect of ABCB1 (rs1045642) C>T gene polymorphism on the PT value