Avilafernandez7198

Cytokines of the IL-12 family show structural similarities but have distinct functions in the immune system. Prominent members of this cytokine family are the pro-inflammatory cytokines IL-12 and IL-23. These two cytokines share cytokine subunits and receptor chains but have different functions in autoimmune diseases, cancer and infections. Accordingly, structural knowledge about receptor complex formation is essential for the development of new therapeutic strategies preventing and/or inhibiting cytokinereceptor interaction. In addition, intracellular signaling cascades can be targeted to inhibit cytokine-mediated effects. Single nucleotide polymorphisms can lead to alteration in the amino acid sequence and thereby influencing protein functions or protein-protein interactions. To understand the biology of IL-12 and IL-23 and to establish efficient targeting strategies structural knowledge about cytokines and respective receptors is crucial. A highly efficient therapy might be a combination of different drugs targeting extracellular cytokinereceptor assembly and intracellular signaling pathways.Methylation is a common structural modification that can alter and improve the biological activities of natural compounds. O-Methyltransferases (OMTs) catalyze the methylation of a wide array of secondary metabolites, including flavonoids, and are potentially useful tools for the biotechnological production of valuable natural products. An OMT gene (PfOMT3) was isolated from perilla leaves as a putative flavonoid OMT (FOMT). Phylogenetic analysis and sequence comparisons showed that PfOMT3 is a class II OMT. Recombinant PfOMT3 catalyzed the methylation of flavonoid substrates, whereas no methylated product was detected in PfOMT3 reactions with phenylpropanoid substrates. Structural analyses of the methylation products revealed that PfOMT3 regiospecifically transfers a methyl group to the 7-OH of flavonoids. These results indicate that PfOMT3 is an FOMT that catalyzes the 7-O-methylation of flavonoids. PfOMT3 methylated diverse flavonoids regardless of their backbone structure. Chrysin, naringenin and apigenin were found to be the preferred substrates of PfOMT3. Gefitinib Recombinant PfOMT3 showed moderate OMT activity toward eriodictyol, luteolin and kaempferol. To assess the biotechnological potential of PfOMT3, the biotransformation of flavonoids was performed using PfOMT3-transformed Escherichia coli. Naringenin and kaempferol were successfully bioconverted to the 7-methylated products sakuranetin and rhamnocitrin, respectively, by E. coli harboring PfOMT3.The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future.The correct assessment of the presence of potentially contaminating elements in soil, as well as in fruits cultivated and harvested from the same places has major importance for both the environment and human health. To address this task, in the case of the Republic of Moldova where the fruit production has a significant contribution to the gross domestic product, the mass fractions of 37 elements (Na, Mg, Al, Ca, Si, K, Mn, Fe, Sc, Ti, V, Cr, Co, Ni, Zn, As, Br, Rb, Sr, Zr, Mo, Cd, Sb, Cs, Ba, La, Ce, Nd, Sm, Eu, Tb, Yb, Hf, Ta, W, Th, and U) were determined by instrumental neutron activation analysis in soil collected from four Moldavian orchards. In the case of three types of fruits, grapes, apples, and plums, all of them collected from the same places, only 22 elements (Na, Mg, Cl, K, Ca, Sc, Mn, Fe, Co, Ni, Cu, Zn, As, Br, Rb, Sr, Sb, Cs, Ba, La, Th, and U) were detected. The enrichment factor, contamination factor, geo-accumulation index, as well as pollution load index were calculated to assess the soil contamination. At the same time, the metal uptake from the soil into fruits was estimated by means of transfer factors. Soil samples showed for almost all elements mass fractions closer to the upper continental crust with the exception of a slightly increased content of As, Br, and Sb, but without overpassing the officially defined alarm thresholds. In the case of fruits, the hazard quotients for all elements with the exception of Sb in fruits collected in two orchards were below unity. A subsequent discriminant analysis allowed grouping all fruits according to their type and provenance.