Xiaomei Yi

Food allergy (FA) is an increasing public health concern, highlighting the urgent need for safe, bioactive-based preventive strategies. This study evaluated genistein, a plant-derived isoflavone, in an ovalbumin (OVA)-induced murine FA model. Genistein was administered before sensitization and throughout allergy induction. Clinical symptoms, rectal temperature, diarrhea, OVA-specific antibodies, mast cell responses, intestinal barrier markers, gut microbiota, short-chain fatty acids (SCFAs), and fecal metabolites were assessed using immunological, histological, microbiome, and metabolomic analyses. Genistein pretreatment prevented OVA-induced clinical symptom scores, rectal temperature decline, diarrhea occurrence, OVA-specific antibody responses, and mast cell responses. These changes were accompanied by preservation of jejunal tight junction-related markers and modulation of T-cell-associated immune responses. In vitro, genistein modulated antigen uptake, maturation-associated features of bone marrow-derived dendritic cells (BMDCs), and BMDC-driven CD4⁺ T-cell polarization. In parallel, genistein-pretreated mice showed altered gut microbial structure, higher relative abundances of selected SCFA-associated taxa, increased fecal butyrate, and fecal metabolomic alterations involving purine metabolism, bile-acid-related metabolism, and tryptophan-related microbial metabolites. Consistently, correlation analyses indicated associations among microbial taxa, metabolites, immune indicators, and intestinal barrier markers. Together, these findings provide preliminary mechanistic insight into genistein in experimental FA and support further investigation of genistein as a dietary bioactive candidate for FA prevention.

Food allergy (FA) is characterized by impaired immune tolerance, intestinal barrier disruption, and gut microbiota dysbiosis. However, whether dietary bioactive compounds such as daidzein can simultaneously modulate these interconnected immune-barrier-microbiota alterations in a preventive context remains poorly understood. The effects and mechanisms of daidzein were systematically investigated in an ovalbumin (OVA)-induced murine FA model through the integration of immunological, histological, and microbiota-metabolite analyses. Results demonstrated that daidzein pretreatment attenuated allergic manifestations and mast-cell activation while shifted toward a T-helper 1 (Th)-biased profile, effectively reducing Th2- and Th17-associated cytokines. Daidzein also strengthened intestinal barrier integrity by upregulating the expression of Claudin-1 and ZO-1. Furthermore, daidzein remodeled the gut microbial community by enriching butyrate-producing genera such as Roseburia, this enrichment was positively associated with elevated fecal butyrate levels. Collectively, these findings highlight the coordinated effects of daidzein on Th-cell-mediated immunity, epithelial barrier function, and microbiota-metabolite profiles, supporting its potential as a dietary candidate for the preventive management of FA in this murine model.

Soybean β-conglycinin (7S) is a major food allergen, and mitigating its allergenicity is critical for food safety. In this study, the potential of glycitein (Gly), a dietary isoflavone, to modulate 7S allergenicity was evaluated. Spectroscopic and molecular-simulation analyses revealed that Gly bound to 7S mainly through hydrogen bonding and van der Waals forces, loosening its conformation to enhance protease accessibility and digestibility. In vitro, Gly moderately reduced IgE binding and significantly decreased β-hexosaminidase and IL-6 release. In vivo, it showed that allergic reactions were weakened, with lower antibody levels in serum and significant suppression of IL-4 in spleen. Gly also partially restored Th1/Th2 balance and modulated gut microbiota composition by normalizing the ratio of Firmicutes/Bacteroidetes while enriching beneficial genera such as Faecalibacterium. Overall, Gly mitigated 7S allergenicity through structural remodeling, enhanced digestibility, and immune-microbiota modulation, highlighting its potential as a functional ingredient for hypoallergenic soy-based foods.

Alzheimer’s disease (AD) is the most common type of dementia. A major pathological feature of AD is the aggregation of amyloid-β (Aβ), primarily driven by β-secretase (BACE1) activity. However, the mechanisms underlying continuous Aβ accumulation remain unclear. Circulating extracellular vesicles (EVs) may play a crucial role in AD progression. Here, we investigate whether circulating EVs in AD promote Aβ generation and aggregation. In this study, we found that compared to WTEVs (circulating EVs isolated from WT mice), APPEVs (circulating EVs isolated from APP/PS1 mice) showed higher concentrations and activated the JAK2-STAT1 pathway in neurons, upregulating BACE1 expression and activity. This cascade promoted amyloid precursor protein (APP) β-cleavage in lipid rafts, inducing substantial Aβ generation. Proteomic analysis revealed complement C1q in APPEVs as a key protein activating the JAK2-STAT1-BACE1 pathway. Furthermore, in vivo experiments demonstrated that intravenously injected APPEVs crossed the blood-brain barrier without damaged the epithelial tight junction, promoting BACE1 expression in neurons, and enhancing Aβ production and aggregation in brain. Inhibition of C1q mitigated these effects in both in vitro and in vivo experiments. In conclusion, during the progression of AD, circulating EVs containing complement C1q are delivered to neurons, activating their JAK2-STAT1 signaling pathway. This activation upregulates the expression of BACE1, subsequently enhancing the β-cleavage of APP in lipid rafts. These events lead to a substantial increase in Aβ production, exacerbating the pathological progression of AD.

Oral administration of synbiotics is a highly effective approach to improve food allergies through the modulation of gut microbiota. Therefore, the effects of synbiotics composed of Lactiplantibacillus plantarum (Lp) and fructo-oligosaccharide (FOS) on soybean-sensitized mice were explored in this study focusing on the gut microbiota and metabolisms. The results indicated that Lp-FOS intervention significantly alleviated allergic symptoms, reduced the IgE, IgG1, and mMCP-1 levels, restored the balance of Th1/Th2 and Tregs/Th17, and enhanced intestinal barrier integrity. 16S rDNA microbiome sequencing revealed that Lp-FOS increased the Lachnospiraceae and Lactobacillus proportions and reduced the Desulfovibrionaceae and Muribaculaceae proportions. Nontargeted metabolomics further demonstrated that Lp-FOS improved gut metabolic disorders by modulating key pathways involved in amino acid metabolism, cofactor and vitamin metabolism, and lipid metabolism, with a notable enhancement in tryptophan metabolism. Collectively, this study confirmed that Lp-FOS could mitigate soybean allergy by regulating the immune system, gut microbiota, and metabolic pathway. This study will offer novel insights into developing synbiotic-based interventions against food allergies.

Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease, affect millions of people worldwide. Tremendous efforts have been put into disease-related research, but few breakthroughs have been made in diagnostic and therapeutic approaches. Extracellular vesicles (EVs) are heterogeneous cell-derived membrane structures that arise from the endosomal system or are directly separated from the plasma membrane. EVs contain many biomolecules, including proteins, nucleic acids, and lipids, which can be transferred between different cells, tissues, or organs, thereby regulating cross-organ communication between cells during normal and pathological processes. Recently, EVs have been shown to participate in various aspects of neurodegenerative diseases. Abnormal secretion and levels of EVs are closely related to the pathogenesis of neurodegenerative diseases and contribute to disease progression. Numerous studies have proposed EVs as therapeutic targets or biomarkers for neurodegenerative diseases. In this review, we summarize and discuss the advanced research progress on EVs in the pathological processes of several neurodegenerative diseases. Moreover, we outline the latest research on the roles of EVs in neurodegenerative diseases and their therapeutic potential for the diseases.

An Enrichment Method For Small Extracellular Vesicles Derived From. JoVE publishes peer-reviewed scientific video protocols to accelerate biological, medical, chemical and physical research. Watch our scientific video articles. JoVE is the world-leading producer and provider of science videos with the mission to improve scientific research, scientific journals, and education. Millions of scientists, educators and students at thousands of universities, colleges, hospitals and biopharmaceutical companies worldwide use JoVE for their research, teaching and learning.

Colorectal cancer (CRC) is a malignancy that seriously threatens human health, and metastasis from CRC is a major cause of death and poor prognosis for patients. Studying the potential mechanisms of small extracellular vesicles (sEVs) in tumor development may provide new options for early and effective diagnosis and treatment of CRC metastasis. In this review, we systematically describe how sEVs mediate epithelial mesenchymal transition (EMT), reconfigure the tumor microenvironment (TME), modulate the immune system, and alter vascular permeability and angiogenesis to promote CRC metastasis. We also discuss the current difficulties in studying sEVs and propose new ideas.

Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related deaths in women worldwide. Currently, patients’ survival remains a challenge in BC due to the lack of effective targeted therapies and the difficult condition of patients with higher aggressiveness, metastasis and drug resistance. Small extracellular vesicles (sEVs), which are nanoscale vesicles with lipid bilayer envelopes released by various cell types in physiological and pathological conditions, play an important role in biological information transfer between cells. There is growing evidence that BC cell-derived sEVs may contribute to the establishment of a favorable microenvironment that supports cancer cells proliferation, invasion and metastasis. Moreover, sEVs provide a versatile platform not only for the diagnosis but also as a delivery vehicle for drugs. This review provides an overview of current new developments regarding the involvement of sEVs in BC pathogenesis, including tumor proliferation, invasion, metastasis, immune evasion, and drug resistance. In addition, sEVs act as messenger carriers carrying a variety of biomolecules such as proteins, nucleic acids, lipids and metabolites, making them as potential liquid biopsy biomarkers for BC diagnosis and prognosis. We also described the clinical applications of BC derived sEVs associated MiRs in the diagnosis and treatment of BC along with ongoing clinical trials which will assist future scientific endeavors in a more organized direction.

Exosomes are a heterogeneous subset of extracellular vesicles (EVs) that biogenesis from endosomes. Besides, exosomes contain a variety of molecular cargoes including proteins, lipids and nucleic acids, which play a key role in the mechanism of exosome formation. Meanwhile, exosomes are involved with physiological and pathological conditions. The molecular profile of exosomes reflects the type and pathophysiological status of the originating cells so could potentially be exploited for diagnostic of cancer. This review aims to describe important molecular cargoes involved in exosome biogenesis. In addition, we highlight exogenous factors, especially autophagy, hypoxia and pharmacology, that regulate the release of exosomes and their corresponding cargoes. Particularly, we also emphasize exosome molecular cargoes as potential biomarkers in liquid biopsy for diagnosis of cancer.