A therapeutic strategy that targets multiple proinflammatory factors in inflammatory bowel disease (IBD) with minimal systemic side effects would be attractive. Here, we develop a drug-free, biodegradable nanomedicine that acts against IBD by scavenging proinflammatory cell-free DNA (cfDNA) and reactive oxygen species (ROS). Polyethylenimine (PEI) was conjugated to antioxidative diselenide-bridged mesoporous organosilica nanoparticles (MONs) to formulate nanoparticles (MON-PEI) that exhibited high cfDNA binding affinity and ROS-responsive degradation. In ulcerative colitis and Crohn’s disease mouse colitis models, orally administered MON-PEI accumulated preferentially in the inflamed colon and attenuated colonic and peritoneal inflammation by alleviating cfDNA- and ROS-mediated inflammatory responses, allowing a reduced dose frequency and ameliorating colitis even after delayed treatment. This work suggests a new nanomedicine strategy for IBD treatment.
Microbiota‐based therapeutics offer innovative strategies to treat inflammatory bowel diseases (IBDs). However, the poor clinical outcome so far and the limited flexibility of the bacterial approach call for improvement. Inspired by the health benefits of probiotics in alleviating symptoms of bowel diseases, bioartificial probiotics are designed to restore the intestinal microenvironment in colitis by regulating redox balance, immune responses, and the gut microbiome. The bioartificial probiotic comprises two components: an E. coli Nissle 1917‐derived membrane (EM) as the surface and the biodegradable diselenide‐bridged mesoporous silica nanoparticles (SeM) as the core. When orally administered, the probiotic‐inspired nanomedicine (SeM@EM) adheres strongly to the mucus layer and restored intestinal redox balance and immune regulation homeostasis in a murine model of acute colitis induced by dextran sodium sulfate. In addition, the respective properties of the EM and SeM synergistically alter the gut microbiome to a favorable state by increasing the bacterial diversity and shifting the microbiome profile to an anti‐inflammatory phenotype. This work suggests a safe and effective nanomedicine that can restore intestinal homeostasis for IBDs therapy.
Chronic diabetic wound healing remains a challenge due to the existence of excessive danger molecules and bacteria in the inflammatory microenvironment. There is an urgent need for advanced wound dressings that target both inflammation and infection. Here, a bioactive hydrogel without loading any anti-inflammatory ingredients is rationally designed to achieve a "Pull− Push" approach for efficient and safe bacteria-infected diabetic wound healing by integrating danger molecule scavenging (Pull) with antibiotic delivery (Push) in the inflammatory microenvironment. The cationic hydrogel, termed the OCMC-Tob/PEI hydrogel, is fabricated by the conjugation of polyethylenimine (PEI) and tobramycin (Tob) on an oxidized carboxymethyl cellulose (OCMC) backbone via the Schiff base reaction with injectable, self-healing, and biocompatible properties. The OCMC-Tob/PEI hydrogel not only displays the remarkable capability of capturing multiple negatively charged danger molecules (e.g., cell-free DNA, lipopolysaccharides, and tumor necrosis factor-α) to ameliorate anti-inflammation effects but also achieves controllable long-term antibacterial activity by the pH-sensitive release of Tob. Consequently, this multifunctional hydrogel greatly expedites the wound closure rate with combined anti-inflammation and anti-infection effects on Pseudomonas aeruginosa-infected diabetic wounds. Our work provides a highly versatile treatment approach for chronic diabetic wounds and a promising dressing for regenerative medicine.
Osteoarthritis is a common multifactorial chronic disease that occurs in articular cartilage, subchondral bone, and periarticular tissue. The pathogenesis of OA is still unclear. To investigate the differences in serum metabolites between OA and the control group, liquid chromatography/mass spectrometry (LC/MS)-based metabolomics was used. To reveal the pathogenesis of OA, 12 SD male rats were randomly divided into control and OA groups using collagenase to induce OA for modeling, and serum was collected 7 days after modeling for testing. The OA group was distinguished from the control group by principal component analysis and orthogonal partial least squares-discriminant analysis, and six biomarkers were finally identified. These biomarkers were metabolized through tryptophan metabolism, glutamate metabolism, nitrogen metabolism, spermidine metabolism, and fatty acid metabolism pathways. The study identified metabolites that may be altered in OA, suggesting a role in OA through relevant metabolic pathways. Metabolomics, as an important tool for studying disease mechanisms, provides useful information for studying the metabolic mechanisms of OA.
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