Disulfiram with Cu2+ alleviates dextran sulfate sodium-induced ulcerative colitis in mice.

Background: Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug for chronic alcohol addiction, has anti-inflammatory effects that help prevent various cancers, and Cu2+ can enhance the effects of DSF. Inflammatory bowel diseases (IBD) are characterized by chronic or recurrent relapsing gastrointestinal inflammation. Many drugs targeting the immune responses of IBD have been developed, but their application has many problems, including side effects and high costs. Therefore, there is an urgent need for new drugs. In this study, we investigated the preventive effects of DSF+Cu2+ on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Methods: The anti-inflammatory effects were investigated using the DSS-induced colitis mouse model and lipopolysaccharide (LPS)-induced macrophages. DSS-induced TCRß-/- mice were used to demonstrate the effect of DSF in conjunction with Cu2+ on CD4+ T cell-secreted interleukin 17 (IL-17). In addition, the effect of DSF+Cu2+ on intestinal flora was studied by 16S rRNA microflora sequencing. Results: DSF and Cu2+ could significantly reverse the symptom of DSS-induced UC in mice, such as weight loss, disease activity index score, colon length shortening, and reversal of colon pathological changes. DSF and Cu2+ could inhibit colonic macrophage activation by blocking the nuclear factor kappa B (NF-κB) pathway, reducing nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3)-inflammasome-derived interleukin 1 beta (IL-1ß) secretion and caspase-1 (CASP1) activation, and decreasing IL-17 secretion by CD4+ T cells. Moreover, the treatment of DSF and Cu2+ could protect the intestinal barrier by reversing the expression of tight junction proteins, zonula occluden-1 (ZO-1), occludin, and mucoprotein-2 (MUC2). Additionally, DSF+Cu2+ could reduce the abundance of harmful bacteria and increase beneficial bacteria in the intestinal tract of mice, effectively improving intestinal microecology. Conclusion: Our study evaluated the effect of DSF+Cu2+ on the immune system and gut microbiota in colonic inflammation and highlighted its potential to treat UC in the clinic.

A Nomogram for Predicting Liver Metastasis of Lymph-Node Positive Luminal B HER2 Negative Subtype Breast Cancer by Analyzing the Clinicopathological Characteristics of Patients with Breast Cancer.

Background: Luminal B-like human epidermal growth factor receptor 2 negative (Luminal B [HER2-]) is the most common molecular subtype of breast cancer (BC). Since the relationship between Luminal B (HER2-) BC and liver metastasis (LM) is poorly defined, this retrospective study aimed to develop an LM risk nomogram for patients with lymph node-related (N + Luminal B [HER2-]) BC. Methods: Data were obtained for patients initially diagnosed with BC from the Tianjin Medical University Cancer Institute and Hospital. There were 30,975 Chinese female patients with stage I-III BC and follow-up confirming 1217 subsequent patients with LM, and 427 patients with N + Luminal B (HER2-). The LM risk was assessed using Cox proportional hazards regression, histogram, Venn diagram, and Kaplan-Meier survival analysis, with further analysis for patients with N + Luminal B (HER2-) BC. A nomogram was established based on the N + Luminal B (HER2-) BC data, which was validated using calibration plots. Results: The median age of 427 patients with N + Luminal B (HER2-) liver metastasis of breast cancer (BCLM) was 49 years. The largest number of patients with BCLM was diagnosed between the second to the 6th year, the longest interval from initial BC diagnosis to subsequent LM was 145 months. The patients with LM as the first site of distant metastasis which is associated with better survival were analyzed by Kaplan-Meier. The nomogram was constructed for the risk of LM that included age, menstrual status, unilateral oophorectomy, pregnancy, hepatitis B antigen, region of residence, tumor size, lymph node, clavicular lymph nodes, progesterone receptor, and lymph vessel invasion. Conclusion: We described the clinicopathological characteristics of patients with stage I-III BC, and constructed a nomogram for calculating personalized LM probabilities for patients with N + Luminal B (HER2-), which could guide future prolonged or early extensive treatment decisions.