Risk of disease flares after SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus.

This study aims to elucidate the effectiveness and safety of SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE). We enrolled uninfected SLE patients who received two vaccine doses (BNT162b2 or mRNA-1273) and historical unvaccinated patients. Neutralizing antibodies, adverse reactions, and disease flares were evaluated 4 weeks after the second vaccination. Ninety patients were enrolled in each group. Among the vaccinated patients, SLE Disease Activity Index (SLEDAI), and prednisolone doses before vaccination were 2, and 5 mg/d, respectively. After the second vaccination, 19 (21.1%) had no neutralizing antibodies. Adverse reactions occurred in 88.9% within 3 d. Negative antibodies were associated with anemia and mycophenolate mofetil administration. SLEDAI increased modestly but significantly after vaccination, with 13 (14.4%) experiencing flares and 4 (4.4%) severe flares (nephritis in three and vasculitis in one). The flare rate was higher in vaccinated patients than unvaccinated controls. The mean duration between the second vaccination and flares was 35 d, and flares occurred at least 8 days after vaccination. Multivariable analysis showed that high SLEDAI and anti-dsDNA antibodies were associated with flares. The vaccine type, neutralizing antibody titer, and adverse reaction frequency did not affect flares. Therefore, residual disease activity before vaccination increases flare risk.

Effects of lysophosphatidic acid (LPA) signaling via LPA receptors on cellular functions associated with ATP reduction in osteosarcoma cells treated with ethidium bromide.

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1 to LPA6) exhibits a variety of malignant properties in cancer cells. Intracellular ATP depletion leads to the development of necrosis and apoptosis. The present study aimed to evaluate the effects of LPA receptor-mediated signaling on the regulation of cancer cell functions associated with ATP reduction. Long-term ethidium bromide (EtBr) treated (MG63-EtBr) cells were established from osteosarcoma MG-63 cells. The intracellular ATP levels of MG63-EtBr cells were significantly lower than that of MG-63 cells. LPAR2, LPAR3, LPAR4 and LPAR6 gene expressions were elevated in MG63-EtBr cells. The cell motile and invasive activities of MG63-EtBr cells were markedly higher than those of MG-63 cells. The cell motile activity of MG-63 cells was increased by LPA4 and LPA6 knockdowns. In cell survival assay, cells were treated with cisplatin (CDDP) every 24 h for 3 days. The cell survival to CDDP of MG63-EtBr cells was lower than that of MG-63 cells. LPA2 knockdown decreased the cell survival to CDDP of MG-63 cells. The cell survival to CDDP of MG-63 cells was inhibited by (2 S)-OMPT (LPA3 agonist). Moreover, the cell survival to CDDP of MG-63 cells was enhanced by LPA4 and LPA6 knockdowns. These results indicate that LPA signaling via LPA receptors is involved in the regulation of cellular functions associated with ATP reduction in MG-63 cells treated with EtBr.

The analysis of an effect of seed propagation on defense strategy against pathogen transmission within clonal plant population using lattice model.

Many clonal plants have two breeding systems, vegetative and seed propagation. In vegetative propagation, plants reproduce genetically identical offspring that have lower mortality rates. By contrast, the seed propagated offspring has higher mortality rate, however, the seed propagation acts an important role in maintaining the genetic diversity and reproduce widely. According to the experimental studies, the balance between the breeding systems, vegetative and seed propagation, is determined by several functions, such as resource allocation. The infection and spread of systemic pathogen also affect the optimal balance of the breeding systems. Thus, we examine the effect of invasion of systemic pathogen on the optimal balance of the breeding systems of clonal plant using lattice model in two cases, single population and mixed population. In the analysis, the equilibrium and its local stability were derived using approximation method and numerical simulation in single population. Additionally, two situations were assumed in mixed population, infected and uninfected populations, and the efficacy of seed propagation on the suppression of epidemic infections was examined by comparing the results in the two situations. As a result, seed propagation is an effective defensive behavior against systemic pathogens. In the single population, the plants increase their population by increasing the proportion of seed propagation when the epidemic pathogen has highly infective. In mixed population, the increasing proportion of seed propagation is the optimal breeding strategy to defend against the spread of a systemic pathogen.

Pathogen Propagation Model with Superinfection in Vegetatively Propagated Plants on Lattice Space.

Many clonal plants have two reproductive patterns, seed propagation and vegetative propagation. By vegetative propagation, plants reproduce the genetically identical offspring with a low mortality, because resources are supplied from the other individuals through interconnected ramets at vegetative-propagated offspring. However, the ramets transport not only resources but also systemic pathogen. Pathogens evolve to establish and spread widely within the plant population. The superinfection, which is defined as the ability that an established pathogen spreads widely by infecting to already-infected individuals with other strains of a pathogen, is important to the evolution of pathogens. We examine the dynamics of plant reproduction and pathogen propagation considering spatial structure and the effect of superinfection on genetic diversity of pathogen by analysis of several models, 1-strain and multiple-strain models, on two-dimensional square lattice. In the analysis of 1-strain model, we derive equilibrium value by mean-field approximation and pair approximation, and its local stability by Routh-Hurwitz stability criterion. In the multiple-strain models, we analyze the dynamics by numerical simulation of mean-field approximation, pair approximation and Monte Carlo simulation. Through the analyses, we show the effect of parameter values to dynamics of models, such as transition of dominant strain of pathogen, competition between plants and pathogens and density of individuals. As a result, (i) The strain with intermediate cost becomes dominant when both superinfection rate and growth rate are low. (ii) The competition between plants and pathogens occurs in the phase of coexistence of various strains by pair approximation and Monte Carlo simulation. (iii) Too high growth rate leads to the decrease of plant population in all models. (iv) Pathogens are easy to maintain their genetic diversity with low superinfection rate. However, if they do not superinfect, the maintenance becomes difficult. (v) When growth rate of plant is low, individuals are very influenced by distant individuals.