Purpose: Berberine (BBR), a major ingredient extracted from Coptis chinensis, is a natural drug with limited oral bioavailability. We developed nanostructured lipid carriers (NLCs) as a delivery system for enhanced anti-inflammatory activity of BBR against ulcerative colitis (UC). Methods: BBR-loaded nanostructured lipid carriers (BBR-NLCs) prepared via high-pressure homogenization were evaluated for particle size, zeta potential, drug entrapment efficiency, drug loading, drug release, toxicity, and cellular uptake. The anti-UC activities of free and encapsulated BBR were evaluated in a DSS-induced acute model of UC in mice. Results: Spherical BBR-NLCs were prepared with a particle size of 63.96± 0.31 nm, a zeta potential of +3.16 ± 0.05 mV, an entrapment efficiency of 101.97± 6.34%, and a drug loading of 6.00± 0.09%. BBR-NLCs showed excellent biocompatibility in vivo. Cellular uptake experiments showed that BBR-NLCs improved uptake of BBR by RAW 264.7 cells and Caco-2 cells. Oral administration of BBR-NLCs significantly alleviated colitis symptoms (DAI, colon length, spleen swelling, MPO activity) through inhibition of NF-κB nuclear translocation, decreased expression of pro-inflammatory cytokines (IL-1β, IL-6, MMP-9, CX3CR1, COX-2, TERT), and increased expression of the tight junction protein ZO-1. Conclusion: BBR-loaded NLCs improved colitis symptoms, which suggested that this may be a novel formulation for treatment of UC.

Sanhuangshu'ai decoction (SH), a traditional Chinese medicine (TCM) prescription, has been safely used to treat diarrhea, dysentery and other inflammatory diseases with little side effect and low cost for thousands of years. However, its mechanism remains elusive. This study was designed to investigate the anti-ulcerative colitis (UC) activity of SH and mechanism by detecting its anti-inflammatory, anti-oxidative, and intervention effects of intestinal flora with the dextran sodium sulfate (DSS)-induced colitis mice. The DSS-induced colitis mice was orally administered SH for 1 week with 0.8 or 1.6 g kg^-1 d^-1 dosage. A clinical disease activity score was evaluated daily. The colonic tissues of the mice were collected and prepared to detect its anti-inflammatory, anti-oxidative, intervention effects of intestinal flora and hydrogen peroxide(H₂O₂) in vivo, cytotoxicity and ROS influencing effects in vitro. Histological colitis severity and expression of cytokines were also determined. Oral administration of SH significantly prevented the development of colitis. It reduced the expression of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in the colon. Moreover, SH administration alleviated the oxidative stress in the colon of DSS-induced colitis mice, evidenced by the decrease of myeloperoxidase (MPO) activity and malondialdehyde (MDA) level, and increase of ROS level. Furthermore, SH can prevent the decrease ofLactobacillus sp. and population abundance of intestinal flora caused by DSS. SH significantly ameliorates the symptoms of DSS-induced colitis mice and the potential mechanism of SH may involve in multiple kinds of metabolic pathway including the regulation of gut microbiota, inflammatory mediators and cytokines.

Lung adenocarcinoma (LUAD) is the most prevalent and aggressive subtype of lung cancer, exhibiting a dismal prognosis with a five-year survival rate below 5%. DEAD-box RNA helicase 18 (DDX18, gene symbol DDX18), a crucial regulator of RNA metabolism, has been implicated in various cellular processes, including cell cycle control and tumorigenesis. However, its role in LUAD pathogenesis remains elusive. This study demonstrates the significant upregulation of DDX18 in LUAD tissues and its association with poor patient survival (from public databases). Functional in vivo and in vitro assays revealed that DDX18 knockdown potently suppresses LUAD progression. RNA sequencing and chromatin immunoprecipitation experiments identified cyclin-dependent kinase 4 (CDK4), a cell cycle regulator, as a direct transcriptional target of DDX18. Notably, DDX18 depletion induced G1 cell cycle arrest, while its overexpression promoted cell cycle progression even in normal lung cells. Interestingly, while the oncogenic protein c-Myc bound to the DDX18 promoter, it did not influence its expression. Collectively, these findings establish DDX18 as a potential oncogene in LUAD, functioning through the CDK4-mediated cell cycle pathway. DDX18 may represent a promising therapeutic target for LUAD intervention.

Background. Huzhentongfeng (HZTF) is an extract from four Chinese medical herbs for treating gout. This study aims to evaluate its antigout activity and preliminary explore its mechanism in vivo and in vitro. Methods. The rats were intragastrically administered with HZTF for 5 days and then injected 0.1 ml (10 mg) of MSU crystals to their joints for generating a gout model to analyze the paw volume and histopathology of joint synovial tissues of rats with different doses. We also investigated the antioxidant capacity of HZTF in vitro using indication including lipid peroxidation, DPPH·, and ABTS⁺ radical-scavenging capacity; besides, we used qRT-PCR to measure the effect of HZTF on interleukin (IL)-1β, caspase-1, NLRP3, and NQO1 expression in hydrogen peroxide-stimulated RAW264.7 macrophages and IL-1β, IL-6, and tumor necrosis factor (TNF)-α in MSU crystal-induced THP-1 monocytes. Confocal microscopy analysis was used to observe the dimerization of ASC adapter proteins. In addition, we also established quality standard of HZTF by using the high-performance liquid chromatography (HPLC) method. Results. HZTF could significantly suppress the paw swelling and neutrophil infiltration induced by MSU intra-articular injection in rats compared with the control group. HZTF also showed inhibition effects of inflammatory cytokines (IL-1β, IL-6, and TNF-α) secretion at 25.00 and 50.00 μg/ml in MSU-induced THP-1 cells but showed no effects of IL-1β, IL-6, and TNF-α mRNA expression in MSU-induced THP-1 cells. Furthermore, confocal microscopy analysis showed that HZTF could prevent the oligomerization of ASC. Moreover, HZTF also showed effects in cell-free and cell-base tests of antioxidant capacity. Conclusion. The results prove that HZTF possessed the potential preventive effect against gout arthritis, and the effect may be attributed to its preventing effect on neutrophil infiltration and proinflammatory cytokines secretion such as IL-1β, IL-6, and TNF-α which were caused by the activation of inflammasome.

Isolating commensal fungi from mouse intestines has been challenging, limiting our understanding of their role in intestinal immune homeostasis and diseases. Using an Fc fusion protein of the C-type lectin receptor Dectin-2, we successfully purified the commensal Ascomycota fungus Engyodontium sp. from mouse feces. Engyodontium enhances the antimicrobial activity of colonic neutrophils via the CARD9 pathway and exacerbates colitis by impairing the colonization of intestinal Lactobacillus johnsonii WXY strain. L . johnsonii produces high levels of l-glutamic acid by expressing the glutaminase-encoding gene glsA to facilitate Treg expansion via enhancing IL-2 receptor signaling. Patients with Crohn disease (CD) and ulcerative colitis harbored increased Engyodontium and decreased L . johnsonii abundance. Engyodontium directly induced calprotectin in human colonic neutrophils, and patients with CD had lower levels of l-glutamic acid, which also promoted human Treg expansion. These findings highlight the Engyodontium -calprotectin axis against the Lactobacillus -glutamate-Treg cascade to aggravate colitis, suggesting commensal Engyodontium -triggered signaling as a therapeutic target for mucosal inflammatory diseases.