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Background: CD226, an activating receptor expressed on the surface of natural killer (NK) cells and T cells, is also seen on B cells and CD226 polymorphism is associated with systemic lupus erythematosus (SLE). Because the specific roles of CD226+ B cells in SLE are still unknown, we investigated the association of CD226+ B cells with SLE. Methods: We measured CD226 expression on B cells and its subsets using flow cytometry in 48 SLE patients and 24 healthy controls (HCs). We assessed the relationships between CD226+ B cells and SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and prognosis after 12 months. Results: The proportions of CD226+ cells in whole B cells and all its subsets were significantly higher in SLE patients than HCs. In SLE patients, the proportions of CD226+ B cells and CD226+ switched-memory (SM) B cells were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers, and negatively correlated with serum complement levels. Moreover, basal percentages of CD226+ B cells and CD226+ SM B cells were low in patients who were in Lupus Low Disease Activity State after 12 months. In patients with renal involvement, the proportion of CD226+ B cells increased. Additionally, the proportion of CD226+ B cells was higher in patients who were not in complete renal remission after 12 months. Conclusions: Increased proportion of CD226+ B cells was associated with disease activity and prognosis of SLE. CD226+ B cells may be a useful biomarker for the management of SLE. [ABSTRACT FROM AUTHOR]

Itis considered that Hoogsteen base pairs and DNA triplex structuresplay important roles in cellular processes even though these structuresare less than duplexes of Watson–Crick base pairs. Molecularions clearly affect the stability of DNA structures in vivo; however,the mechanisms are unknown. Here, we investigated the effects of sodiumions, choline ions, and tetramethylammonium ions on DNA triplexesusing molecular dynamics simulations. We found that nonpolar interactions,which are associated with van der Waals interactions, and solvent-accessiblesurface area were more important than polar or electrostatic interactionsin determining the affinity of a molecular cation for the DNA grooveareas. The free energy gain due to a cation that fit optimally withina DNA groove was larger than the free energy loss due to the effectof dehydration. Cations with shapes complementary to that of a particularDNA groove configuration stabilized triplex formation, but cationsthat disturbed hydrogen bonds between DNA bases were destabilizing.These stabilizing and destabilizing mechanisms of molecular cationswere also applicable to a DNA duplex composed of Watson–Crickbase pairs. The molecular-level view of cation interactions with DNAstructures will guide the design of DNA devices, DNA-based drugs,and genetic therapies. [ABSTRACT FROM AUTHOR]

Underphysiological conditions, G–C base pairs are morestable than A–T base pairs. In a previous study, we showedthat in the hydrated ionic liquid of choline dihydrogen phosphate,the stabilities of these base pairs are reversed. In the present study,we elucidated the unique binding interactions of choline ions withDNA atoms from a microscopic viewpoint using molecular dynamics simulations.Three times more choline ions bind to the DNA duplex than sodium ions.Sodium ions bind closely but not stably; in contrast, the cholineions bind through multiple hydrogen bonding networks with DNA atomsstably. The affinity of choline ion for the minor groove of A–Tbase pairs is more than 2 times that for other groove areas. In thenarrow A–T minor groove, choline ion has high affinity forthe ribose atoms of thymine. Choline ions also destabilize the formationof hydrogen bonds between G–C base pairs by binding to baseatoms preferentially for both of duplex and single-strand DNA, whichare associated with the bonds between G–C base pairs. Our newfinding will not only lead to better control of DNA stability foruse in DNA nanodevices, but also provide new insight into the stabilityof DNA duplexes under crowding conditions found in living cells. [ABSTRACT FROM AUTHOR]

The instability of Hoogsteen base pairs relative to Watson-Crick base pairs has limited biological applications of triplex-forming oligonucleotides. Hydrated ionic liquids (ILs) provide favourable environments for a wide range of chemical reactions and are known to impact the stabilities of Watson- Crick base pairs. We found that DNA triplex formation was significantly stabilized in hydrated choline dihydrogen phosphate as compared with an aqueous buffer at neutral pH. Interestingly, the stability of Hoogsteen base pairs was found to be comparable with that of Watson-Crick base pairs in the hydrated IL. Molecular dynamics simulations of a DNA triplex in the presence of choline ions revealed that the DNA triplex was stabilized because of the binding of choline ion around the third strand in the grooves. Our finding will facilitate the development of new DNA materials. Our data also indicate that triplex formation may be stabilized inside cells where choline ions and their derivatives are abundant in vivo. [ABSTRACT FROM AUTHOR]

Background: CD226, an activating receptor expressed on the surface of natural killer (NK) cells and T cells, is also seen on B cells and CD226 polymorphism is associated with systemic lupus erythematosus (SLE). Because the specific roles of CD226 + B cells in SLE are still unknown, we investigated the association of CD226 + B cells with SLE., Methods: We measured CD226 expression on B cells and its subsets using flow cytometry in 48 SLE patients and 24 healthy controls (HCs). We assessed the relationships between CD226 + B cells and SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and prognosis after 12 months., Results: The proportions of CD226 + cells in whole B cells and all its subsets were significantly higher in SLE patients than HCs. In SLE patients, the proportions of CD226 + B cells and CD226 + switched-memory (SM) B cells were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers, and negatively correlated with serum complement levels. Moreover, basal percentages of CD226 + B cells and CD226 + SM B cells were low in patients who were in Lupus Low Disease Activity State after 12 months. In patients with renal involvement, the proportion of CD226 + B cells increased. Additionally, the proportion of CD226 + B cells was higher in patients who were not in complete renal remission after 12 months., Conclusions: Increased proportion of CD226 + B cells was associated with disease activity and prognosis of SLE. CD226 + B cells may be a useful biomarker for the management of SLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nakano, Ayano, Kushimoto, Kawano, Higashioka, Inokuchi, Mitoma, Kimoto, Akahoshi, Ono, Arinobu, Akashi, Horiuchi and Niiro.)