A model of pregnancy-associated malaria for inducing adverse pregnancy outcomes in ICR mouse.

BACKGROUND: Based on understanding of placental pathological features and safe medication in pregnancy-associated malaria (PAM), establishment of a stable pregnant mouse infection model with Plasmodium was urgently needed. METHODS: ICR mice with vaginal plugs detected were randomly divided into post-pregnancy infection (Malaria+) and uninfected pregnancy (Malaria-) cohorts. Age-matched mice that had not been mated were infected as pre-pregnancy infection group (Virgin control), which were subsequently mated with ICR males. All mice were inoculated with 1 × 106Plasmodium berghei ANKA-infected RBCs by intraperitoneal injection, and the same amount of saline was given to Malaria- group. We recorded the incidence of adverse pregnancy outcomes and the amounts of offspring in each group. RESULTS: The Virgin group mice were unable to conceive normally, and vaginal bleeding, abortion, or stillbirth appeared in the Malaria+ group. The incidence of adverse pregnancy outcomes was extremely high and statistically significant compared with the control (Malaria-) group (P < 0.05), of which placenta exhibited pathological features associated with human gestational malaria. CONCLUSIONS: The intraperitoneal injection of 1 × 106Plasmodium berghei ANKA-infected RBCs could establish a model of pregnancy-associated malaria in ICR mouse.

Homeostasis of Arabidopsis R protein RPS2 is negatively regulated by the RING-type E3 ligase MUSE16.

The homeostasis of resistance (R) proteins in plants must be tightly regulated to ensure precise activation of plant immune responses upon pathogen infection, while avoiding autoimmunity and growth defects when plants are uninfected. It is known that CPR1, an F-box protein in the SCF E3 complex, functions as a negative regulator of plant immunity through targeting the resistance (R) proteins SNC1 and RPS2 for degradation. However, whether these R proteins are also targeted by other E3 ligases is unclear. Here, we isolated Arabidopsis MUSE16, which encodes a RING-type E3 ligase, from a forward genetic screen and suggest that it is a negative regulator of plant immunity. Unlike CPR1, knocking out MUSE16 alone in Arabidopsis is not enough to result in defense-related dwarfism, since only RPS2 out of the tested R proteins accumulated in the muse16 mutants. Thus, our study identifies a novel E3 ligase involved in the degradation of nucleotide-binding and leucine-rich repeat (NLR) R proteins, support the idea that ubiquitin-mediated degradation is a fine-tuned mechanism for regulating the turnover of R proteins in plants, and that the same R protein can be targeted by different E3 ligases for regulation of its homeostasis.

Erythrocyte membrane with CLIPPKF as biomimetic nanodecoy traps merozoites and attaches to infected red blood cells to prevent Plasmodium infection.

BACKGROUND: Malaria remains a serious threat to global public health. With poor efficacies of vaccines and the emergence of drug resistance, novel strategies to control malaria are urgently needed. RESULTS: We developed erythrocyte membrane-camouflaged nanoparticles loaded with artemether based on the growth characteristics of Plasmodium. The nanoparticles could capture the merozoites to inhibit them from repeatedly infecting normal erythrocytes, owing to the interactions between merozoites and heparin-like molecules on the erythrocyte membrane. Modification with a phosphatidylserine-targeting peptide (CLIPPKF) improved the drug accumulation in infected red blood cells (iRBCs) from the externalized phosphatidylserine induced by Plasmodium infection. In Plasmodium berghei ANKA strain (pbANKA)-infected C57BL/6 mice, the nanoparticles significantly attenuated Plasmodium-induced inflammation, apoptosis, and anemia. We observed reduced weight variation and prolonged survival time in pbANKA-challenged mice, and the nanoparticles showed good biocompatibility and negligible cytotoxicity. CONCLUSION: Erythrocyte membrane-camouflaged nanoparticles loaded with artemether were shown to provide safe and effective protection against Plasmodium infection.

Efficacy and Safety of Qinghao Biejia Decoction in the Treatment of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aimed to systematically assess the therapeutic efficacy and safety of Qinghao Biejia decoction combined with conventional chemical medicine in patients with systemic lupus erythematosus (SLE), and to provide reference for clinical medication. Methods: Multiple databases were retrieved by computer for randomized controlled trials (RCTs) of treating SLE with Qinghao Biejia decoction combining chemical medicine, from the establishment of the database to January 2021. Study screening, data collection, and quality assessment were performed independently by two reviewers. RevMan 5.4 and Stata 15.1 software were used for Meta-analysis. Results: Nine eligible studies, involving 655 SLE participants, were included. Meta-analysis showed that the additional use of Qinghao Biejia decoction superior to chemical medicine alone in people with SLE in improving the overall response rate (RR = 1.30, 95% CI [1.19, 1.41], p < 0.00001, heterogeneity p = 0.61, I 2 = 0%), and can decrease SLE Disease Activity Index (SLEDAI) and TCM symptom scores, improve immunological indexes (C3, C4, IgG, IgA, IFN-γ, IL-4, Th1/Th2), reduce the occurrence of adverse events in treatment (P ≤ 0.05). Conclusion: Based on this meta-analysis, the additional use of Qinghao Biejia decoction has more advantages in the treatment of SLE than conventional chemical medication alone, which could enhance the efficacy and reduce adverse reactions, and is worthy of clinical promotion. However, more and higher quality RCTs are still need to confirm our findings.

The Roles of Environmental Factors in Regulation of Oxidative Stress in Plant.

Exposure to a variety of environmental factors such as salinity, drought, metal toxicity, extreme temperature, air pollutants, ultraviolet-B (UV-B) radiation, pesticides, and pathogen infection leads to subject oxidative stress in plants, which in turn affects multiple biological processes via reactive oxygen species (ROS) generation. ROS include hydroxyl radicals, singlet oxygen, and hydrogen peroxide in the plant cells and activates signaling pathways leading to some changes of physiological, biochemical, and molecular mechanisms in cellular metabolism. Excessive ROS, however, cause oxidative stress, a state of imbalance between the production of ROS and the neutralization of free radicals by antioxidants, resulting in damage of cellular components including lipids, nucleic acids, metabolites, and proteins, which finally leads to the death of cells in plants. Thus, maintaining a physiological level of ROS is crucial for aerobic organisms, which relies on the combined operation of enzymatic and nonenzymatic antioxidants. In order to improve plants' tolerance towards the harsh environment, it is vital to reinforce the comprehension of oxidative stress and antioxidant systems. In this review, recent findings on the metabolism of ROS as well as the antioxidative defense machinery are briefly updated. The latest findings on differential regulation of antioxidants at multiple levels under adverse environment are also discussed here.

Sumoylation, Phosphorylation, and Acetylation Fine-Tune the Turnover of Plant Immunity Components Mediated by Ubiquitination.

Ubiquitination-mediated protein degradation plays a crucial role in the turnover of immune proteins through rapid alteration of protein levels. Specifically, the over-accumulation of immune proteins and consequent activation of immune responses in uninfected cells is prevented through degradation. Protein post-translational modifications can influence and affect ubiquitination. There is accumulating evidence that suggests sumoylation, phosphorylation, and acetylation differentially affect the stability of immune-related proteins, so that control over the accumulation or degradation of proteins is fine-tuned. In this paper, we review the function and mechanism of sumoylation, phosphorylation, acetylation, and ubiquitination in plant disease resistance responses, focusing on how ubiquitination reacts with sumoylation, phosphorylation, and acetylation to regulate plant disease resistance signaling pathways. Future research directions are suggested in order to provide ideas for signaling pathway studies, and to advance the implementation of disease resistance proteins in economically important crops.