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Immunoglobulin E (IgE)-mediated food allergy has been dramatically increasing in incidence over the last few decades. The combinations of both genetic and environmental factors that affect the microbiome and immune system have demonstrated significant roles in its pathogenesis. The morbidity, and at times mortality, that occurs as the result of this specific, reproducible, but impaired immune response is due to the nature of the shift from a regulatory T (Treg) cellular response to a T helper 2 (Th2) cellular response. This imbalance caused by food allergens results in an interleukin (IL)-4 and IL-13 dominant environment that drives B cell activation and differentiation into IgE-producing plasma cells. The resulting symptoms can range from mild to more severe anaphylaxis, and even death. Current therapeutic strategies involve avoidance and broad symptom management upon accidental exposure; however, no definitive cure exists. This narrative review highlights how the elucidation of the pathogenesis of IgE-mediated food allergy resulted in the development of therapeutics that are more specific to these individual receptors and molecules which have been relatively successful in mitigating this potentially life-threatening allergic response. However, potential adverse effects and re-sensitization following the conclusion of treatment has urged the need for improved therapeutic methods. Therefore, given the understanding of their mechanism of action and the overlap with the mechanism of IgE-mediated food allergies, probiotics and small molecule natural compounds may provide novel therapeutic and preventative strategies. This is compelling, as they have demonstrated success in clinical trials and may provide hope to improve quality of life in allergy patients. [ABSTRACT FROM AUTHOR]

Rationale: Approximately 32 million people in the United States suffer from food allergies. Some food groups, such as legumes – peanuts, tree nuts, fish, and shellfish, have a high risk of cross-reactivity. However, the murine model of multiple food group cross-reactivity is limited. Objective: We sought to develop a murine model that can be used to investigate novel therapeutics for the treatment of multiple food allergies. Methods: C3H/HeJ mice were sensitized intraperitoneally (i.p.) once a week for three weeks with a mixture of 500µg of protein from peanut, cashew, walnut, shrimp, cod, and 2 mg Alum. The control group consisted of naïve mice. IgE levels against the sensitized allergens and their cross-reactive allergens were measured by ELISA at baseline and 3 weeks after sensitization. In weeks 4 and 5, the mice were given intragastric challenges with 200mg/mouse of each food: peanut, chickpea, lentil, cashew, almond, pistachio, hazelnut, brazil nut, walnut, pecan, shrimp, lobster, cod, salmon, and mackerel. After each challenge, anaphylactic symptoms, rectal temperatures, and plasma histamine were measured. Results: There was a significant elevation of IgE against sensitized antigens (peanut cashew, walnut, shrimp, and cod) as well as cross-reactive allergens used for oral food challenge from legumes including peanut, chickpea, and lentil, as well as tree nuts such as cashew, almond, pistachio, hazelnut, brazil nut, walnut, and pecan. Furthermore, there was a significant increase in crustaceans such as shrimp, lobster and fish like cod, salmon, and mackerel (p <0.01). Consistently, significantly increased anaphylactic symptom scores (p <0.05), decreased rectal temperature (p <0.001), and increased plasma histamine (p <0.05) compared to the naïve mice occurred following each challenge with sensitized foods and unsensitized, but cross-reactive foods. Conclusion: We generated a comprehensive murine model of IgE-mediated multiple food groups of cross-reactive anaphylaxes. This will provide an essential tool for developing novel therapies for cross-reactivity multiple food allergies. [ABSTRACT FROM AUTHOR]

Simple Summary: Investigation of cancer biomarkers for prognostic, diagnostic, and therapeutic applications has enhanced patient outcomes in hematological and solid cancer types. Cancer biomarkers are discovered by evaluating genetic dysregulation compared to normal samples. Homeobox genes, genes that are key players during embryonic development, have been shown to have dysregulated expression patterns in multiple cancer types. Therefore, this review covers the dysregulation of HOX genes and their encoded factors and the HOX family's role as potential cancer biomarkers. The HOX gene family encodes for regulatory transcription factors that play a crucial role in embryogenesis and differentiation of adult cells. This highly conserved family of genes consists of thirty-nine genes in humans that are located in four clusters, A–D, on different chromosomes. While early studies on the HOX gene family have been focused on embryonic development and its related disorders, research has shifted to examine aberrant expression of HOX genes and the subsequent implication in cancer prediction and progression. Due to their role of encoding master regulatory transcription factors, the abnormal expression of HOX genes has been shown to affect all stages of tumorigenesis and metastasis. This review highlights the novel role of the HOX family's clinical relevance as both prognostic and diagnostic biomarkers in hematological and solid tumors. [ABSTRACT FROM AUTHOR]

Pathologic mast cells and basophils, key effector cells in allergic reactions, play pivotal roles in initiating and perpetuating IgE-mediated allergic responses. Conventional therapies for allergies have limitations, prompting exploration into alternative approaches such as small-molecule natural compounds derived from botanical sources. This review synthesizes the existing literature on the effects of these compounds on pathologic mast cells and basophils, highlighting their potential in allergy management, and utilizes the PubMed database for literature acquisition, employing keyword-based searches to identify relevant peer-reviewed sources. Additionally, mechanistic insights were evaluated to contextualize how small-molecule natural compounds can inhibit mast cell/basophil activation, degranulation, and signaling pathways crucial for IgE-mediated allergic reactions. Small-molecule natural compounds exhibit promising anti-allergic effects, yet despite these findings, challenges persist in the development and translation of natural compound-based therapies, including bioavailability and standardization issues. Future research directions include optimizing dosing regimens, exploring synergistic effects with existing therapies, and employing systems pharmacology approaches for a holistic understanding of their mechanisms of action. By harnessing the therapeutic potential of small-molecule natural compounds, effective treatments for allergic diseases may be realized, offering hope for individuals with allergies. [ABSTRACT FROM AUTHOR]

Atopic eczema patients exhibit high levels of Staphylococcus aureus (S. aureus) skin colonization. S. aureus can stimulate macrophages and the expression of proinflammatory cytokines. Berberine (BBR), an alkaloid, attenuates S. aureus toxin production. This study investigated if BBR suppressed bacterial growth and inflammatory response induced by eczema-patient-derived S. aureus using murine macrophage (RAW 264.7) and human monocyte cell lines (U937). RAW 264.7 and U937 were treated with BBR at different concentrations and stimulated with heat-killed S. aureus (ATCC #33591) or S. aureus derived from severe eczema patients (EC01–EC10), who were undergoing topical steroid withdrawal, for 24 h. TNF-α protein levels were determined by ELISA, gene expression by qRT-PCR, cell cytotoxicity by trypan blue excursion, and reactive oxygen species (ROS) levels by fluorometric assay. BBR showed a bacteriostatic effect in S. aureus (ATCC strain #33591 and clinical isolates (EC01–EC10) and suppressed TNF-α production in RAW 264.7 and U937 cells exposed to heat-killed S. aureus (ATCC and clinical isolates) dose-dependently without any cell cytotoxicity. BBR (20 µg/mL) suppressed >90% of TNF-α production (p < 0.001), downregulated genes involved in inflammatory pathways, and inhibited S. aureus ROS production in U937 and RAW 264.7 cells (p < 0.01). BBR suppresses S. aureus-induced inflammation via inhibition of TNF-α release, ROS production, and expression of key genes involved in the inflammatory pathway. [ABSTRACT FROM AUTHOR]