Therapeutic potential of gene therapy for gastrointestinal diseases: Advancements and future perspectives.

Advancements in understanding the pathogenesis mechanisms underlying gastrointestinal diseases, encompassing inflammatory bowel disease, gastrointestinal cancer, and gastroesophageal reflux disease, have led to the identification of numerous novel therapeutic targets. These discoveries have opened up exciting possibilities for developing gene therapy strategies to treat gastrointestinal diseases. These strategies include gene replacement, gene enhancement, gene overexpression, gene function blocking, and transgenic somatic cell transplantation. In this review, we introduce the important gene therapy targets and targeted delivery systems within the field of gastroenterology. Furthermore, we provide a comprehensive overview of recent progress in gene therapy related to gastrointestinal disorders and shed light on the application of innovative gene-editing technologies in treating these conditions. These developments are fueling a revolution in the management of gastrointestinal diseases. Ultimately, we discuss the current challenges (particularly regarding safety, oral efficacy, and cost) and explore potential future directions for implementing gene therapy in the clinical settings for gastrointestinal diseases.

Edible exosome-like nanoparticles from portulaca oleracea L mitigate DSS-induced colitis via facilitating double-positive CD4+CD8+T cells expansion.

Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we isolated and identified Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) from edible Portulaca oleracea L, which exhibited desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4 mV). Oral administration of PELNs effectively suppressed the expressions of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1ß) and myeloperoxidase (MPO), increased levels of the anti-inflammatory cytokine (IL-10), and alleviated acute colitis in dextran sulfate sodium (DSS)-induced C57 mice and IL-10-/- mice. Notably, PELNs exhibited excellent stability and safety within the gastrointestinal tract and displayed specific targeting to inflamed sites in the colons of mice. Mechanistically, oral administration of PELNs played a crucial role in maintaining the diversity and balance of gut microbiota. Furthermore, PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which might activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells. This activation downregulated Zbtb7b expression, leading to the reprogramming of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells). In conclusion, our findings highlighted the potential of orally administered PELNs as a novel, natural, and colon-targeted agent, offering a promising therapeutic approach for managing UC. Schematic illustration of therapeutic effects of oral Portulaca oleracea L -derived natural exosome-like nanoparticles (PELNs) on UC. PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells leading to downregulate the expression of Zbtb7b, reprogram of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells), and decrease the levels of pro-inflammatory cytokines.

Application of Nanoparticles in the Diagnosis of Gastrointestinal Diseases: A Complete Future Perspective.

The diagnosis of gastrointestinal (GI) diseases currently relies primarily on invasive procedures like digestive endoscopy. However, these procedures can cause discomfort, respiratory issues, and bacterial infections in patients, both during and after the examination. In recent years, nanomedicine has emerged as a promising field, providing significant advancements in diagnostic techniques. Nanoprobes, in particular, offer distinct advantages, such as high specificity and sensitivity in detecting GI diseases. Integration of nanoprobes with advanced imaging techniques, such as nuclear magnetic resonance, optical fluorescence imaging, tomography, and optical correlation tomography, has significantly enhanced the detection capabilities for GI tumors and inflammatory bowel disease (IBD). This synergy enables early diagnosis and precise staging of GI disorders. Among the nanoparticles investigated for clinical applications, superparamagnetic iron oxide, quantum dots, single carbon nanotubes, and nanocages have emerged as extensively studied and utilized agents. This review aimed to provide insights into the potential applications of nanoparticles in modern imaging techniques, with a specific focus on their role in facilitating early and specific diagnosis of a range of GI disorders, including IBD and colorectal cancer (CRC). Additionally, we discussed the challenges associated with the implementation of nanotechnology-based GI diagnostics and explored future prospects for translation in this promising field.

Exploring the efficacy of herbal medicinal products as oral therapy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses a collection of idiopathic diseases characterized by chronic inflammation in the gastrointestinal (GI) tract. Patients diagnosed with IBD often experience necessitate long-term pharmacological interventions. Among the multitude of administration routes available for treating IBD, oral administration has gained significant popularity owing to its convenience and widespread utilization. In recent years, there has been extensive evaluation of the efficacy of orally administered herbal medicinal products and their extracts as a means of treating IBD. Consequently, substantial evidence has emerged, supporting their effectiveness in IBD treatment. This review aimed to provide a comprehensive summary of recent studies evaluating the effects of herbal medicinal products in the treatment of IBD. We delved into the regulatory role of these products in modulating immunity and maintaining the integrity of the intestinal epithelial barrier. Additionally, we examined their impact on antioxidant activity, anti-inflammatory properties, and the modulation of intestinal flora. By exploring these aspects, we aimed to emphasize the significant advantages associated with the use of oral herbal medicinal products in the treatment of IBD. Of particular note, this review introduced the concept of herbal plant-derived exosome-like nanoparticles (PDENs) as the active ingredient in herbal medicinal products for the treatment of IBD. The inclusion of PDENs offers distinct advantages, including enhanced tissue penetration and improved physical and chemical stability. These unique attributes not only demonstrate the potential of PDENs but also pave the way for the modernization of herbal medicinal products in IBD treatment.

Stem cell-derived intestinal organoids: a novel modality for IBD.

The organoids represent one of the greatest revolutions in the biomedical field in the past decade. This three-dimensional (3D) micro-organ cultured in vitro has a structure highly similar to that of the tissue and organ. Using the regeneration ability of stem cells, a 3D organ-like structure called intestinal organoids is established, which can mimic the characteristics of real intestinal organs, including morphology, function, and personalized response to specific stimuli. Here, we discuss current stem cell-based organ-like 3D intestinal models, including understanding the molecular pathophysiology, high-throughput screening drugs, drug efficacy testing, toxicological evaluation, and organ-based regeneration of inflammatory bowel disease (IBD). We summarize the advances and limitations of the state-of-the-art reconstruction platforms for intestinal organoids. The challenges, advantages, and prospects of intestinal organs as an in vitro model system for precision medicine are also discussed. Key applications of stem cell-derived intestinal organoids. Intestinal organoids can be used to model infectious diseases, develop new treatments, drug screens, precision medicine, and regenerative medicine.