Hyaluronic acid/inulin-based nanocrystals with an optimized ratio of indigo and indirubin for combined ulcerative colitis therapy via immune and intestinal flora regulation.

Indigo (IND) and indirubin (INB) have demonstrated a synergistic effect in treating ulcerative colitis at a ratio of 7.5:1. However, the colon mucus layer, a critical physiological barrier against external threats, is also a biological barrier, limiting the potential for effective drug delivery to the lamina propria for regulating inflammatory cells. Inspired by the potential of Hyaluronic acid (HA), to enhance cellular uptake by inflammatory cells, and Pluronic® F127 (F127), known for overcoming the mucus barrier, this study innovatively developed INB/IND nanosuspensions by co-modifying with F127 and HA. Moreover, inulin serves a dual purpose as a spray protective agent and a regulator of intestinal flora. Therefore, it was incorporated into INB/IND nanosuspensions for subsequent spray drying, resulting in the preparation of INB/IND nanocrystals (INB/IND-NC). The mucus penetration of INB/IND-NC was 24.30 times that of the control group. Besides, INB/IND-NC exhibited enhanced cellular uptake properties proximately twice that of Raw INB/IND. Importantly, INB/IND-NC exhibited improved therapeutic efficacy in DSS-induced mice by regulating the expression of cytokines, regulating immune responses via downregulating the expression of macrophages, neutrophils, and dendritic cells and maintaining intestinal flora homeostasis. Our study provides a new perspective for applying natural products for treating inflammatory diseases.

Dual role of the nasal microbiota in neurological diseases-An unignorable risk factor or a potential therapy carrier.

Recently, comparative studies have rapidly increased with the closer correlation between microbiota and neurological diseases. However, most insights about the association between microbiota and neurological diseases still focus on the gut-brain axis and ignore that nasal microbiota could form a complex and essential link with the nervous system via the nose-to-brain pathway, suggesting the role in modulating the immune system, metabolic system, and nervous system development, which influence the physiopathology of neurological diseases. Due to the complex interactions between nasal microbiota and the brain, the nasal microbiota may have a particular pathogenic effect and therapeutic potential on neurological diseases. Therefore, this review aims to deeply analyze the dual effects of nasal microbiota on neurological diseases, focusing on pathogenic and therapeutic effects to provide a new perspective for preventing and treating neurological diseases by altering nasal microbiota. This review concludes the bidirectional effects of nasal microbiota on neurological diseases, including the pathogenicity and potential treatment on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Stroke. Furthermore, modern medical technology combined with artificial intelligence, including implantable sensors, modeling software, and nanofluid techniques, may further study the complex effects between nasal microbiota and the brain, thereby providing new options for treating neurological diseases.