The Role of the Immune System in the Course of Hashimoto's Thyroiditis: The Current State of Knowledge.

The process of thyroid autoimmunization develops against the background of genetic predispositions associated with class II human leukocyte antigens (HLA-DR), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and forkhead transcription box protein P3 (FOXP3). Environmental factors, such as vitamin D deficiency, Zn, Se, and Mg, as well as infections, chronic stress, pregnancy, smoking, alcohol, medications, intestinal dysbiosis, and malnutrition, also play an important role. The first stage of autoimmunization involves the accumulation of macrophages and dendritic cells, as well as plasma cells. In the second stage, the mutual interactions of individual cells in the immune system lead to a decrease in the level of CD8+ in favor of CD4+, which intensifies the synthesis of T lymphocyte derivatives, especially Th1, Th17, Tfh, and Tc, reducing the level of Treg. Consequently, the number of the anti-inflammatory cytokines IL10 and IL2 decreases, and the synthesis of the pro-inflammatory cytokines IL-2, Il-12, Il-17, IL-21, IL-22, IFN-γ, and TNF-α increases. The latter two especially trigger the pyroptosis process involving the inflammasome. Activation of the inflammasome by IL-ß and IL-18 produced by macrophages is one of the mechanisms of pyroptosis in the course of Hashimoto's thyroiditis, involving Gram-negative bacteria and NLRC4. In the next step, the apoptosis of thyroid cells is initiated by the intensification of perforin, granzyme, and proteoglycan synthesis by Tc and NK cells. The current findings raise many possibilities regarding interventions related to the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines produced by both T and B lymphocytes. Furthermore, since there is currently no effective method for treating thyroid autoimmunity, a summary of the review may provide answers regarding the treatment of not only Hashimoto's thyroiditis, but also other autoimmune diseases associated with autoimmunity.

Conformational preferences of guanine-containing threose nucleic acid building blocks in B3LYP studies.

In this paper, detailed and systematic gas-phase B3LYP conformational studies of four monomers of threose nucleic acid (TNA) with guanine attached at the C1' atom and bearing different substituents (OH, OP(=O)OH2 and OCH3) in the C2' and C3' positions of the α-l-threofuranose moiety are presented. All exocyclic single-bond (χ, ε and γ) rotations, as well as the ν0-ν4 endocyclic torsion angles, were taken into consideration. Three (threoguanosines TG1-TG3) or two (TG4) energy minima were found for the rotation about the χ torsion angle. The syn orientation (the A rotamer family) is strongly privileged in geometries TG1 and TG2, whereas the anti orientation (the C rotamer family) and the syn orientation are observed to be in equilibrium (with populations of 56% and 44%, respectively) for TG3. In the case of TG4, the high-anti orientation (the B rotamer family) turned out to be by far the most favourable, with the contribution exceeding 90% in equilibrium. Such a preference can be attributed to the inability of H-bonding between sugar and nucleobase and possibly because of the steric strains. The low-energy conformers of TG1-TG4 occupy the northeastern (P âˆ¼ 40°) and/or southern (P âˆ¼ 210°) parts of the pseudorotational wheel, which fits the A- and B-type DNA helices quite well. Additionally, in the case of TG4, some relatively stable geometries have the furanoid ring in conformation lying on the northwestern part of the pseudorotational wheel (P âˆ¼ 288°).