Persistent airway inflammation, bronchoconstriction, and hyperresponsiveness constitute the defining characteristics of allergic airway disease (AAD). haspinkinase signal Exogenous interleukin-10 (IL-10) alleviates allergic inflammation, but its half-life is comparatively short.The protective effect of a cell membrane coating on nanomaterials has been proven to preserve therapeutic payloads and boost treatment efficacy.A novel macrophage-based nanoparticle drug's effectiveness in treating house dust mite (HDM)-induced allergic airway diseases was the focus of this investigation.Encapsulated within alveolar macrophage cell membranes were IL-10-poly(lactic-co-glycolic acid (PLGA) nanoparticles. A mouse model of allergic airway disease was constructed via the repeated inhalation of HDM extracts. Treatments applied to the mice included free IL-10, IL-10 packaged within PLGA nanoparticles (IL10-NP), or IL-10 incorporated into nanoparticles, further coated with membranes from alveolar macrophages (IL10-AMNP). To gauge the therapeutic outcomes, airway hyperresponsiveness, lung inflammation, cytokine concentrations, and the proportion of regulatory T cells (Treg) to T-helper 17 (Th17) cells were measured.Treatment with IL10-AMNP, in contrast to the use of standard IL-10, was more effective in reducing airway hyperresponsiveness, decreasing T-helper 2 (Th2)/Th17 cytokine levels, and suppressing the recruitment of neutrophils and eosinophils to the airways in HDM-induced mouse models. In addition, a considerable improvement in the balance of Tregs and Th17 cells was observed in groups receiving IL10-AMNP treatment.This study highlighted the efficacy of PLGA nanoparticle cores, featuring alveolar macrophage cell membrane coatings, in transporting therapeutic cytokines to the lungs, ultimately improving the balance between Tregs and Th17 cells. These findings indicate that macrophage-based nanoparticle drugs may prove to be a beneficial approach in treating allergic airway diseases.This study demonstrated that therapeutic cytokines, delivered by PLGA nanoparticle cores wrapped with alveolar macrophage cell membranes, successfully reached the lungs and improved the homeostatic balance between Tregs and Th17 cells. These research findings suggest that macrophage-nanoparticle drug combinations provide a promising avenue for treating allergic airway diseases.A proclivity for blood clots, frequently linked to severe cases of Coronavirus disease 2019 (COVID-19), is a recognized consequence of the infection. The prothrombotic effects of neutrophils releasing neutrophil extracellular traps (NETs) along with the hyperactivity of platelets, have so far, only partially explained COVID-19-associated coagulopathy (CAC). An in-depth comprehension of the reciprocal actions of platelets and neutrophils in the pathophysiology of CAC is still not fully developed. A rare autoimmune condition, vaccine-induced thrombotic thrombocytopenia (VITT), is linked to the creation of auto-antibodies in reaction to vaccination with adenoviral vector vaccines. Life-threatening thromboembolic events, a characteristic feature of VITT, are associated with high fatality rates. Due to the relatively recent discovery of thrombophilia in VITT, enhanced comprehension of the condition can be instrumental in improving patient management and prevention strategies. This review undertakes the task of summarizing the current state of knowledge on how platelets and neutrophils work together in COVID-19 and VITT.A dynamic family of transcription factors, the FOXO class O proteins, are represented by the four members FOXO1, FOXO3, FOXO4, and FOXO6. FOXO family members, functioning as both context-dependent transcriptional activators and repressors, control a variety of cellular processes, including the pausing of the cell cycle, programmed cell death, metabolic activity, extended lifespan, and cell type specification. Negative regulation of FOXO activity by the PI3K-AKT signaling pathway empowers cell proliferation and survival. FOXO family activity is finely tuned by distinct kinases, with positive influence exerted by JNK and AMPK, and negative influence by ERK-MAPK and CDK2, along with the further influence of post-translational modifications. Empirical findings point to FOXOs' capacity as genuine tumor suppressors, by manipulating cellular behavior including cell cycle arrest and apoptosis via transcriptional control. In contrast, an alternative model has emerged, suggesting that FOXOs play a role as mediators of cellular balance and/or resistance in both healthy and pathological states. The distinct members of the FOXO family have unique roles in the typical maturation and function of B cells, and aberrant expression and mutations of FOXOs are now recognized as features of discrete B-cell malignancies. The beneficial role of active FOXO function in disease prevention, exemplified in chronic lymphocytic leukemia, unfortunately reverses in diffuse large B-cell lymphoma, where FOXO expression is connected with disease progression, an observation extending to additional forms of cancer. The debate surrounding FOXO proteins' dual roles in disease progression centers on the specific conditions favoring or hindering progression, and the therapeutic viability of targeting FOXO-driven mechanisms in B-cell malignancies. This work explores the distinct functions of FOXO family members within B-cell lineages, investigates the regulatory factors impacting FOXO function, primarily through post-translational modifications, and speculates on the potential for developing future therapies targeting FOXO activity.Ovarian dysfunction and insulin resistance associated with polycystic ovary syndrome (PCOS) are modulated by the gut microbiota and its metabolic products.A genetically-engineered probiotic, EcN, is characterized by its superb safety record in human use, effectively targeting metabolic and immune system disorders rooted in gut microbiome dysfunction. Our investigation centered on exploring the effects and application of probiotic EcN on the interplay between gut microbiota, metabolism, IL-22, and mitochondrial damage in PCOS.Dehydroepiandrosterone (DHEA)-induced PCOS mice underwent treatment with either EcN, FMT, or IL-22 inhibitors. Individuals with polycystic ovary syndrome (PCOS) and those categorized as clinically controlled were chosen for further investigation. ELISA and biochemical assays were employed to quantify sex hormones, insulin, glucose, cholesterol, and inflammatory factors in serum and follicular fluid supernatants. The pathological alterations present within the ovarian tissues were apparent through the application of HE staining. Analysis of JC-1 levels and COX4 gene expression in granulosa cells was performed using ELISA and RT-qPCR techniques. The western blot procedure was used to evaluate the presence of progesterone receptor A (PR-A), LC3II/I, Beclin1, p62, and CytC. The presence and quantity of autophagosomes in granulosa cells were determined through electron microscopy. To examine the alterations in gut microbiota and metabolism, 16S rRNA sequencing and LC-MS/MS were applied.By improving sex hormone levels and ovarian architecture, EcN treatment promoted the production of IL-22, COX4, and PR-A in granulosa cells, while suppressing mitophagy in PCOS mice. EcN's influence manifested as a reduction in the number of gut microbiota and a marked increase in the density of some microbial species.,,andPolycystic ovarian syndrome presents itself in mice. EcN treatment resulted in improved metabolic disorders in PCOS mice, specifically within the amino sugar and nucleotide sugar metabolic pathways. IL-22's presence was positively correlated with certain conditions.,Progesterone is inversely proportional to .The following are essential elements: luteinizing hormone, testosterone, N-acetylglucosamine, L-fucose, and N-acetylmannosamine, each contributing uniquely. FMT's results showed that EcN lessened mitochondrial impairment in granulosa cells from PCOS mice, with gut microbiota playing a role in this effect, but this was reversed by the application of an IL-22 inhibitor. Studies in clinical trials on PCOS patients have shown reduced quantities of IL-22 and mitochondrial damage in granulosa cells.EcN's intervention, improving sex hormone balance and ovarian morphology, along with suppressing gut microbiota and modulating amino and nucleotide sugar metabolism, significantly improved IL-22 levels and diminished mitochondrial damage in granulosa cells of PCOS mice.By promoting the restoration of sex hormone levels and ovarian tissue structure, EcN mitigated IL-22 levels and mitochondrial damage in granulosa cells of PCOS mice, while concurrently modulating gut microbiota and regulating amino sugar and nucleotide sugar metabolism.Transcriptional activation is a consequence of the collaborative action of chromatin modifiers that modify the epigenetic landscape to become permissive. While histone 3 lysine 9 (H3K9) methylation is widely recognized as a mechanism for gene repression, the supporting evidence for H3K9 demethylases in gene activation is currently limited.Utilizing a combination of JMJD2d/Kdm4d knockdown and overexpression in mouse embryonic fibroblasts, complemented by thorough epigenomic analyses, we determined the role of histone 3 lysine 9 demethylases in the innate immune system's response.The H3K9 demethylase, Kdm4d/JMJD2d, is shown to positively regulate responses mediated by type I interferons. Decreased levels of JMJD2d in mouse embryonic fibroblasts (MEFs) results in a lessened transcriptional response, causing heightened vulnerability to viruses; conversely, higher levels of the demethylase trigger a more powerful interferon activation. JMJD2d's role in type I interferon responses involves modulating both enhancer RNA transcription and the dynamic distribution of H3K9me2 at related promoters. To corroborate these results, we demonstrate that JMJD2d is positioned at enhancer elements across the genome before stimulation, but translocates to inducible promoters upon the initiation of transcriptional activation.JMJD2d, as indicated by our comprehensive data, acts as a chromatin modifier, bridging enhancer transcription with promoter demethylation and thereby modulating transcriptional responses.