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1.
Mol Ther ; 32(4): 890-909, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38369751

ABSTRACT

Long-term use of conventional drugs to treat inflammatory bowel diseases (IBD) and colitis-associated cancer (CAC) has an adverse impact on the human immune system and easily leads to drug resistance, highlighting the urgent need to develop novel biotherapeutic tools with improved activity and limited side effects. Numerous products derived from plant sources have been shown to exert antibacterial, anti-inflammatory and antioxidative stress effects. Plant-derived vesicle-like nanoparticles (PDVLNs) are natural nanocarriers containing lipids, protein, DNA and microRNA (miRNA) with the ability to enter mammalian cells and regulate cellular activity. PDVLNs have significant potential in immunomodulation of macrophages, along with regulation of intestinal microorganisms and friendly antioxidant activity, as well as overcoming drug resistance. PDVLNs have utility as effective drug carriers and potential modification, with improved drug stability. Since immune function, intestinal microorganisms, and antioxidative stress are commonly targeted key phenomena in the treatment of IBD and CAC, PDVLNs offer a novel therapeutic tool. This review provides a summary of the latest advances in research on the sources and extraction methods, applications and mechanisms in IBD and CAC therapy, overcoming drug resistance, safety, stability, and clinical application of PDVLNs. Furthermore, the challenges and prospects of PDVLN-based treatment of IBD and CAC are systematically discussed.


Subject(s)
Colitis-Associated Neoplasms , Colitis , Inflammatory Bowel Diseases , Nanoparticles , Animals , Humans , Colitis-Associated Neoplasms/complications , Colitis-Associated Neoplasms/drug therapy , Colitis-Associated Neoplasms/metabolism , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/etiology , Anti-Inflammatory Agents/pharmacology , Macrophages/metabolism , Colitis/etiology , Colitis/complications , Mammals
2.
Front Immunol ; 12: 623451, 2021.
Article in English | MEDLINE | ID: mdl-33679767

ABSTRACT

Multiple sclerosis is a chronic autoimmune disease involving the central nervous system, and shows a high disability rate. Its pathogenesis is complicated, and there is no good treatment. In recent years, with in-depth studies on the regulation of gastrointestinal flora, the relationship between the mammalian immune system and the intestinal flora has been extensively explored. Changes in the composition and structure of the gastrointestinal flora can affect the characteristics and development of the host immune system and even induce a series of central nervous system inflammation events. The occurrence and development of multiple sclerosis are closely related to the continuous destruction of the intestinal barrier caused by intestinal dysbacteriosis. In this study, we analyzed Lactobacillus acidipiscis in a mouse model of experimental autoimmune encephalomyelitis (EAE). We found that the amount of L. acidipiscis in the intestinal tract was inversely proportional to the progress of EAE development. In addition, the number of CD4+ FOXP3+ regulatory T cells in the mesenteric lymph nodes of mice increased significantly after the mice were fed with L. acidipiscis, and the differentiation of CD4+ T cells to Th1 and Th17 cells was inhibited. However, the protective effect of L. acidipiscis was lost in γδ T cell-deficient mice and hence was concluded to depend on the presence of regulatory γδ T cells in the intestinal epithelium. Moreover, including L. acidipiscis enhanced the development of Vγ1+γδ T cells but suppressed that of Vγ4+γδ T cells. In summary, our results demonstrated the ability of L. acidipiscis to induce generation of regulatory γδ T cells that suppress the development of the encephalomyelitic Th1 and Th17 cells and the progress of EAE.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/prevention & control , Gastrointestinal Microbiome , Intestinal Mucosa/microbiology , Intraepithelial Lymphocytes/microbiology , Lactobacillus/immunology , Probiotics , Animals , Cell Differentiation , Cytokines/metabolism , Disease Models, Animal , Dysbiosis , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/microbiology , Female , Genes, T-Cell Receptor gamma , Host-Pathogen Interactions , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intraepithelial Lymphocytes/immunology , Intraepithelial Lymphocytes/metabolism , Lactobacillus/growth & development , Mice, Inbred C57BL , Mice, Knockout , Phenotype , Th1 Cells/immunology , Th1 Cells/metabolism , Th1 Cells/microbiology , Th17 Cells/immunology , Th17 Cells/metabolism , Th17 Cells/microbiology
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