Campsummers4376

Artemisinins are secondary metabolites of the medicinal plant Artemisia annua, have anti-inflammatory, anticarcinogenic, immunomodulating, antimicrobial and other properties. However, the pharmacokinetics, pharmacodynamics, exact molecular targets of artemisinin are not well known. The interaction of artemisinin with human serum albumin was studied both in vitro and in silico, and compared with dexamethasone. The quenching of the fluorescence emission of human serum albumin with artemisinin at different temperatures proceeded according to a single mechanism and indicated the static nature, which is similar to the effect of dexamethasone. Selleck EGFR inhibitor Artemisinin and dexamethasone interact with Drug site I on human serum albumin. We have shown for the first time the formation of hydrogen bond with Arg218, which plays a crucial role in the binding of drugs at site I. Dexamethasone forms hydrogen bonds with the side chain of Arg218 and Arg222 and the main chain of Val343. The amino acids of subdomains IIA and IIIA of human serum albumin coincide for both compounds. Studies of the electrophoretic mobility of DNA of sarcoma S-180 cells show that artemisinin does not interact directly with DNA. Therefore, we assume that one of the main transporters of artemisinin is human serum albumin. Moreover, the interaction parameters of artemisinin with human serum albumin coincide with those of dexamethasone.In this paper, the property of the muscle titin protein to form in vitro specific amyloid-like aggregates is discussed. The main difference from the known amyloid aggregates is the formation of a quaternary structure that resembles cross-β, with no changes in the secondary structure. Based on the results obtained earlier, as well as the results of this study, we make assumptions about changes in the structure of titin that occur during the formation of amyloid-like aggregates. In particular, our X-ray diffraction data on the titin aggregates suggest that β-strands in the aggregates of this protein are not located perpendicular to the fibril axis, as described for other amyloid proteins, but in parallel. The distance between the β-sheets in the aggregates may vary, and the β-sheets themselves are not strictly oriented along one of the axes, which can lead to the appearance of a diffuse ring reflection of ~8-12 Å. In this regard, the titin aggregates should not be called amyloid, but amyloid-like, with a quaternary structure that resembles cross-β. It cannot be excluded that the formation of this quaternary structure can also occur due to the partial unfolding of titin domains, followed by the interaction of open β-strands between neighboring domains and/or domains of neighboring molecules.A test of the sensitivity of seven colon cancer cell lines to a panel of 12 nonpathogenic human enteroviruses revealed significant differences in the ability of tumor cells to become infected and replicate different viral strains. Among the factors that can affect the sensitivity of cells to viruses are differences in the state of the mechanisms of antiviral protection, associated with a reaction to type I interferons. Using the two colon cancer cell lines CaCo2 and LIM1215 as a model, significant differences were revealed in the ability of cells to defend themselves against virus infection after 16 hours of treatment with 1000 units/mL of interferon-alpha. To study the effect of the state of the interferon response system, represented by the Jak/STAT signaling pathway, on the sensitivity of cells to different strains of enteroviruses, HEK293T cell lines were used. These are capable of supporting replication of each of the tested enteroviruses, as well as maintaining the ability to protect against viral infection after the treatment with interferon. Using the CRISPR/Cas9 system, HEK293T sublines with knockouts of the IFNAR1 and STAT2 genes were obtained. The sensitivity of control and knockout cells to infection with five strains of enteroviruses and the vesicular stomatitis virus was analyzed. It was noted that knockout of the IFNAR1 and STAT2 genes resulted in an increased sensitivity to all tested viruses. In knockout cells, the levels of reproduction of the vaccine derived of poliovirus type 1, Echoviruses 7 and 30, and Coxsackie viruses B5 and A7 were also significantly increased in comparison with the control HEK293T cells. Thus, deficiencies in the Jak/STAT signaling pathway in tumor cells lead to an overall increase in the sensitivity to oncolytic viruses.Chronic myeloid leukemia is a clonal hematopoietic stem cell disease characterized by myeloid expansion. The hallmark of the disease is the Philadelphia chromosome, which results in the formation of the BCR-ABL oncogene, a tyrosine kinase that is involved in many signaling pathways including Wnt signaling. The latter has a unique role in chronic myeloid leukemia progression; activated signaling leads to the establishment of an additional leukemic stem cell population derived from granulocyte-macrophage progenitors. sFRP1 is an inhibitor of Wnt signaling and its expression is important for differentiation and maintenance of hematopoietic stem cells. In this study, we aimed to investigate miRNAs that target Wnt signaling by being co-induced along with the expression of sFRP1 in K562 cells. We present a detailed analysis of hsa-mir-221 -3p, hsa-mir-222-3p, hsa-mir-106b-5p, hsa-let-7f-5p, hsa-mir-182-5p, hsa-mir-191-5p, and hsa-mir-183-5p and their target genes and their involvement in Wnt signaling.Age-related changes in telomere length (TL) in somatic tissues are not limited only to shortening. It is known that many organisms show different TL dynamics. Such species specificity indicates the complexity of the mechanisms involved in the regulation of TL. Owing to their morphological, physiological, and ecological features, Baikal planarians are an interesting model for studying the TL dynamics and the factors influencing it in comparison with species living outside Baikal. In this work, we investigated telomerase activity and age-related changes in TL in three endemic species of planarians from the Dendrocoelidae family. Two species are giant deep-water species (7-12 cm long, Sorocelis hepatizon and Rimacephalus arecepta), and one is a coastal shallow species (1 cm long, Baikalobia guttata). In addition, we investigated the telomere biology in another small Siberian species from the Planariidae family (2 cm in length, Phagocata sibirica), which is not found in Baikal. TL and telomerase activity were determined using real-time PCR and the TRAP method.