Liver injury can lead to severe acute liver failure and even death in patients. Artesunate (ART), which is a derivative of artemisinin that has been approved by the FDA for the treatment of malaria, has significant regulatory effects on cell death and inflammation. In this study, we found that ART exerts a protective effect on various preclinical animal models of liver injury, including mouse models of liver injury induced by APAP, CCl4, and Con A. Mechanistically, CETSA, DARTS and SPR indicate that ART directly binds to the LYS653 and ASP837 residues within the HECT domain of NEDD4L, and enhances the interaction between NEDD4L and the substrate TXNIP, promoting the ubiquitination and proteasomal degradation of TXNIP, ultimately alleviating APAP-induced liver injury. Furthermore, the overexpression of TXNIP as well as the global knockout or liver-specific knockdown of NEDD4L eliminates the effect of ART on alleviating liver injury. These data suggest that the NEDD4L-TXNIP axis participates in the development of liver injury and highlight the potential of ART to be used in the clinical treatment of liver injury.

Ulcerative colitis (UC) is a recurrent, chronic disease whose main symptoms include weight loss, diarrhea, and blood in the stool. In recent years, the incidence of UC has been increasing year by year, which seriously affects the daily life of patients. Luteolin (Lut), as a flavonoid, is widely found in a variety of vegetables and fruits and has been shown to have a variety of pharmacological activities. This work investigated the effects of Lut on dextrose sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice, with a special focus on the role of endoplasmic reticulum (ER) stress in this. The outcomes demonstrated that colitis symptoms, including disease phenotype, elevated inflammatory factor levels, intestinal barrier damage, and gut microbiota disruption, were considerably alleviated in UC model mice treated with luteolin. Also, Lut alleviated ER stress and apoptosis in UC mice. We then explored the effects of Lut on ER stress and apoptosis induced by thapsigargin (TG) and tunicamycin (TM) in HT29 cells in vitro. It was found that Lut treatment inhibited TM/TG-induced ER stress and apoptosis. However, these inhibitory effects of Lut were attenuated by SIRT1 silencing in TM-treated HT29 cells. In conclusion, our results suggest that Lut supplementation in a mouse model of colitis improves the symptoms of colitis in mice, which provides a theoretical basis for further application of Lut in the prevention of inflammation-related diseases in humans.

Skin cutaneous melanoma (SKCM) arises from melanocytes and is an aggressive form of skin cancer. If left untreated, most melanomas will metastasize, posing a major health risk. GADD45B, a member of the GADD45 family, is known to be involved in DNA damage repair; however, its specific role in SKCM remains largely unclear. In this study, we comprehensively investigated the function of GADD45B in SKCM. By integrating 26 SKCM-related datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), cBioPortal for Cancer Genomics (cBioPortal), Gene Expression Omnibus (GEO), and other databases, we conducted functional enrichment, immune infiltration, and single-cell analyses using R. Additionally, transcriptome sequencing of 30 human SKCM cell lines, phenotype characterization of 29 SKCM lines in vitro, and macrophage polarization analysis were performed. We found that GADD45B expression was significantly downregulated in SKCM patients compared to normal controls (p < 0.001), and higher GADD45B levels correlated with better prognosis (p < 0.05). GADD45B also showed high diagnostic accuracy, with an area under the curve (AUC) of 0.986. GO and KEGG analyses revealed a strong association between GADD45B and immune-related pathways. Gene Set Variation Analysis (GSVA) and single-cell sequencing suggested that GADD45B may serve as a novel immune checkpoint, predominantly expressed in macrophages and promoting M1 polarization. In vitro, overexpression of GADD45B significantly inhibited SKCM cell proliferation, potentially via suppression of the PI3K/Akt signaling pathway, and also reduced chemotherapy resistance. Furthermore, in vivo experiments using a xenograft mouse model demonstrated that GADD45B overexpression significantly suppressed tumor growth. Mice injected with GADD45B-overexpressing tumor cells exhibited smaller tumor volumes from day 15 onwards compared to controls, with markedly reduced tumor volume and weight at the endpoint. These results underscore the potential of GADD45B as an effective tumor suppressor in SKCM. In conclusion, our findings highlight GADD45B as a key regulator in SKCM progression, capable of restraining tumor cell proliferation and enhancing apoptosis. GADD45B holds promise as a novel diagnostic and prognostic biomarker and a potential target for SKCM immunotherapy.

Ulcerative colitis (UC) significantly impairs quality of life and incurs substantial economic costs. Apigenin, a flavonoid abundant in fruits and vegetables, has demonstrated potential in UC management. Utilizing DSS-induced UC mouse models and LS 174 T goblet cell models, this study elucidates apigenin's protective mechanisms. Dietary supplementation with 40 mg/kg apigenin markedly alleviated UC symptoms. Antibiotic-mediated microbiota depletion confirmed that apigenin's efficacy is independent of gut microbiota. Mechanistically, apigenin enhances SERCA2 expression to maintain intracellular calcium homeostasis, thereby inhibiting excessive activation of the PERK-eIF2α-ATF4-CHOP pathway, reducing goblet cell apoptosis, and preserving mucosal barrier integrity. These findings provide a robust theoretical foundation for apigenin as a dietary supplement in the prevention and mitigation of colitis.

Ulcerative colitis (UC) is incurable, and rational dietary interventions are important in preventing UC. Kombucha is a fermented beverage that originated in China and has a variety of activities, including antioxidant, antibacterial and hypoglycemic activities. The aim of this study was to analyze the protective effect of Kombucha polysaccharide (KP) against UC and determine its mechanism of action. The results showed that KP intervention was effective in alleviating dextran sulfate sodium salt (DSS)-induced colitis symptoms and inhibiting DSS-induced inflammation and oxidative stress. Moreover, KP was able to reduce intestinal permeability, promote the expression of tight junction proteins, and help maintain thrush cell numbers and promote mucus secretion. The 16S rDNA results indicated that KP intervention increased the abundance of Rikenellaceae_RC9_gut_group and Clostridiales_unclassified. Untargeted metabolomics techniques revealed that KP can reverse DSS-induced disorders in intestinal metabolism. This study demonstrated that KP alleviated DSS-induced colitis by helping maintain intestinal barrier integrity, regulating the gut microbiota and remodeling metabolism pathways. The findings provide a theoretical basis for the application of KP as a dietary supplement for the prevention of UC.

The prevalence of inflammatory bowel disease (IBD) is progressively rising each year, emphasizing the significance of implementing rational dietary interventions for disease prevention. Oats, being a staple agricultural product, are abundant in protein content. This study aimed to investigate the protective effects and underlying mechanisms of oat peptides (OPs) in a mouse model of acute colitis induced by dextran sulfate sodium salt (DSS) and a Caco-2 cell model. The findings demonstrated that intervention with OPs effectively mitigated the symptoms associated with DSS-induced colitis. The physicochemical characterization analysis demonstrated that the molecular weight of the OPs was predominantly below 5 kDa, with a predominant composition of 266 peptides. This study provides further evidence of the regulatory impact of OPs on the Keap1-Nrf2 signaling axis and elucidates the potential role of WGVGVRAERDA as the primary bioactive peptide responsible for the functional effects of OPs. Ultimately, the results of this investigation demonstrate that OPs effectively mitigate DSS-induced colitis by preserving the integrity of the intestinal barrier and modulating the Keap1-Nrf2 axis. Consequently, these findings establish a theoretical foundation for the utilization of OPs as dietary supplements to prevent the onset of IBD.

Ulcerative colitis (UC) is a chronic noninfectious intestinal disease that severely affects patients’ quality of life. Agaricus blazei Murrill polysaccharide (ABP) is an effective active ingredient extracted from Agaricus blazei Murrill (ABM). It has good efficacy in inhibiting tumor cell growth, lowering blood pressure, and improving atherosclerosis. However, its effect on colitis is unclear. The aim of this study was to analyze the protective effects and potential mechanisms of ABP against dextran sulfate sodium (DSS)-induced acute colitis in mice. The results showed that dietary supplementation with ABP significantly alleviated DSS-induced colitis symptoms, inflammatory responses, and oxidative stress. Meanwhile, ABP intervention was able to maintain the integrity of the intestinal mechanical barrier by promoting the expression of ZO-1 and Occludin tight junction proteins and facilitating mucus secretion. Moreover, 16S rRNA sequencing results suggested that ABP intervention was able to alleviate DSS-induced gut microbiota disruption, and nontargeted metabolomics results indicated that ABP was able to remodel metabolism. In conclusion, these results demonstrate that dietary supplementation with ABP alleviated DSS-induced acute colitis by maintaining intestinal barrier integrity and remodeling metabolism. These results improve our understanding of ABP function and provide a theoretical basis for the use of dietary supplementation with ABP for the prevention of ulcerative colitis.