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关键词： antigen presentation   food allergy   IL-9   MHC class II   mucosal mast cell  

摘要： Background IgE-mediated food allergy is accompanied by mucosal mast cell (MMC) hyperplasia in the intestinal mucosa. Intestinal MMC numbers correlate with the severity of food allergy symptoms. However, the mechanisms by which MMCs proliferate excessively are poorly understood. Here, we clarify the role of newly identified MHC class II (MHCII)-expressing MMCs in the effector phase of IgE-mediated food *** Mice reconstituted with MHCII-deficient or wild-type MMCs were used to generate a mouse mode of IgE-mediated food allergy. We assessed the extent of intestinal MMC hyperplasia and the severity of hypothermia in these mice. In addition, we performed in vitro antigen presentation assay using induced MHCII-expressing MMCs generated from bone marrow cells to evaluate the effect of CD4+ T cell activation on MMC *** In food-allergic mice, we identified the appearance of MHCII-expressing MMCs in the intestinal mucosa and showed that MMC hyperplasia was suppressed in mice with MHCII-deficient MMCs compared to mice with wild-type MMCs. In vitro assays demonstrated that MHCII-expressing MMCs incorporate food antigens directly and through the high-affinity IgE receptor Fc epsilon RI-mediated endocytosis and activate antigen-specific CD4+ T cells from food-allergic mice by antigen presentation. Activated CD4+ T cells secrete IL-4 and large amounts of IL-5, which enhance production of the mast cell growth factor IL-9 by IL-33-activated MMCs. Excess IL-9 causes excessive MMC proliferation, leading to the development of MMC *** Antigen presentation to CD4+ T cells by MHCII-expressing MMCs triggers intestinal MMC hyperplasia and exacerbates IgE-mediated food allergy.

关键词： Acute kidney injury   Multi-omics integration   Therapeutic target discovery   Drug repurposing  

摘要： Acute kidney injury (AKI) remains a critical condition with limited pharmacological options. Bioactive molecules, including cytokines, receptors, and enzymes, play central roles in AKI pathogenesis, but systematic efforts to identify translational targets remain limited. In this study, we implemented a multi-omics integrative framework to nominate and validate candidate targets for AKI. Using genetically informed screens anchored on a curated set of potentially actionable genes, we identified five prioritized candidates, CD46, IL6R, KLRC1, LEAP2, and SMOX, with strong biological plausibility and therapeutic potential. Bulk and single-cell RNA sequencing data revealed cell-type-specific enrichment, particularly in proximal tubules, immune subsets, and endothelium under AKI conditions. Pathway enrichment highlighted shared involvement in cytokine signaling, antigen presentation, and metabolic stress responses. In silico drug repurposing revealed several clinically approved compounds (e.g., tacrine, raloxifene hydrochloride, tretinoin) with strong predicted binding to CD46, IL6R, and SMOX. In vivo experiments demonstrated that pharmacological inhibition of SMOX significantly alleviated tubular injury, preserved renal function, and reduced oxidative stress. In vitro studies further confirmed the protective effects of SMOX inhibition by maintaining epithelial cell integrity and viability in renal tubular cells, while suppressing oxidative damage.

关键词： Guselkumab   inflammatory bowel diseases   mirikizumab   risankizumab   anti-IL23p19  

摘要： A wide range of advanced therapies has become available in recent years for the treatment of moderate-to-severe inflammatory bowel disease (IBD). Among these, monoclonal antibodies targeting the interleukin 23 p19 subunit (anti-IL23p19) have emerged as a promising therapeutic class. Pivotal Phase 3 trials have demonstrated their favorable clinical efficacy and safety in both Crohn's disease (CD) and ulcerative colitis (UC). Three such agents, Risankizumab, Mirikizumab, and Guselkumab, have now been approved in CD and UC. For gastroenterologists, the ability to rationally select among these options to personalize treatment and maximize patient benefit is critical. Key factors to consider when selecting an anti-IL23p19 agent include patient preference regarding mode of administration, IBD phenotype, presence of coexisting extra-intestinal manifestations, concomitant immune-mediated diseases, and previous advanced-therapy exposure. Our review summarizes the current clinical evidence on anti-IL23p19 therapies and provides practical guidance on their use in IBD clinical management, including dosing strategies, choice of dose in CD and UC, and clinical positioning across patients. Finally, anti-IL23p19 inhibition may represent a future first-line therapy option for moderate-to-severe IBD, particularly in patients with concomitant IL-23 driven comorbidities such as psoriasis. Its use in combination with other advanced therapies in selected patients is being explored to enhance therapeutic efficacy and improve long-term outcomes. Further real-world studies are needed to assess its effectiveness and benefits in complex disease phenotypes, including perianal fistulizing Crohn's disease.

关键词： Pulmonary arterial hypertension   Broiler   Transcriptomics   Network pharmacology   Piperine  

摘要： Pulmonary arterial hypertension (PAH) is a chronic, progressive vasculopathy characterized by a sustained elevation in pulmonary vascular resistance and remodeling of pre-capillary pulmonary arterioles, leading to right ventricular failure and often death. This study explores the potential of piperine, a bioactive dietary alkaloid, in mitigating PAH pathogenesis using a broiler chicken model. Network pharmacology analysis identified the IL-6/ STAT3 signaling pathway as key anti-PAH targets of piperine. In vivo experiments demonstrated that piperine treatment significantly reduced PAH-associated mortality, suppressed inflammatory cytokine production, and attenuated pulmonary vascular remodeling in the chicken model. Mechanistically, the observed protective effects were linked to the downregulation of IL-6 expression and STAT3 phosphorylation, along with the suppression of NF-kappa B p65 activation. Furthermore, piperine inhibited hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) in vitro, reinforcing its role in preventing vascular remodeling. Collectively, these findings underscore the potential of piperine as a functional food component with cardiopulmonary protective properties, proposing its utility as a potential dietary intervention for the management of PAH.

关键词： compaction   layered intrusion   microstructure   Il & iacute   maussaq  

摘要： Crystal-melt separation is a fundamental process in magmatic differentiation that has implications for volcanic eruptions and ore deposit formation. However, the mechanical processes governing how crystals and melt separate, which are important for the timescales of melt segregation, are debated. Geochemical and theoretical studies commonly cite viscous compaction, i.e. gravitationally or intrinsic stress-driven deformation of the crystal pile, as a key mechanism of crystal-melt separation. Critically, viscous compaction should produce a microstructural record of internal crystal deformation and crystal alignment that allows us to diagnose its role, if any, in crystal-melt separation. Here, we provide novel textural and microstructural data from the Il & iacute;maussaq complex, a layered alkaline intrusion in South Greenland, and explore whether, and if so through what processes, crystal-melt separation within the crystal pile. Stratigraphically variable disequilibrium and nucleation microstructures within our samples record the vertical migration of interstitial volatile-rich liquid through igneous layers. We observe some mineral bending associated with asymmetrical crystal growth, but no evidence of extensive viscous grain deformation, indicating that viscous compaction was not a significant mechanism in crystal-melt separation for Il & iacute;maussaq. Instead, we suggest that mechanical compaction via crystal rearrangement, accompanied by volatile-rich liquid migration, primarily facilitates crystal-melt separation in intrusions with chemically evolved compositions. Our study shows that post-cumulus crystal repacking and volatile-rich liquid movement impact primary igneous layering in terms of microstructures, modal abundances of main and minor phases as well as phase compositions, therefore potentially controlling the distribution and concentration of rare earth element deposits within layered alkaline intrusions.

关键词： SVM classifier   Biosensor   IL-10 protein detection   LPFG   Mach-Zehnder interferometer  

摘要： Currently, techniques such as machine learning (ML), derived from great technological progress, play a fundamental role in different areas, from finance, marketing, security, education, transportation to science and health. The latter, with the growth in the development of sensors and biosensors, technological tools such as ML allow systems to learn, extract, analyze and classify useful information from the signals they receive. Biosensors, being devices that convert biological signals into quantifiable data, generate a large volume of information, which becomes difficult to interpret manually, but can be processed more efficiently through ML. Support vector machine (SVM), is a supervised machine learning technique, used for classification, regression and even outliers detection, especially useful in the context of biosensors to classify them into different biological states forming a discriminant analysis. This work focuses on the study of SVM as a classifying technique, applied to optical fiber biosensors for the detection of Interleukin 10 (IL-10) due to its role as a neuroprotector protein. Serum samples from ischemic, and ischemic treated with estradiol benzoate (EB) male rats were evaluated at 2 h post-ischemia. In this work we show the performance of SVM on the measured responses of three optical fiber biosensor that are based on a tapered, long period grating and Mach-Zehnder interferometer. The results demonstrate that SVM technique is a good alternative to determine the IL-10 expression on serum sample of a murine model.