Dimethyl fumarate alleviates allergic asthma by strengthening the Nrf2 signaling pathway in regulatory T cells.

Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of allergic asthma. Here, we have evaluated the anti-inflammatory impact of dimethyl fumarate (DMF) in allergic asthma with more focus on determining its effect on T cell responses in allergic asthma. By utilizing the ovalbumin (OVA)-induced allergic asthma model, we observed that DMF administration reduced the allergic asthma symptoms and IgE levels in the OVA-induced mice model. Histopathological analysis showed that DMF treatment in an OVA-induced animal model eased the inflammation in the nasal and bronchial tissues, with a particular decrease in the infiltration of immune cells. Additionally, RT-qPCR analysis exhibited that treatment of DMF in an OVA-induced model reduced the expression of inflammatory cytokine (IL4, IL13, and IL17) while augmenting anti-inflammatory IL10 and Foxp3 (forkhead box protein 3). Mechanistically, we found that DMF increased the expression of Foxp3 by exacerbating the expression of nuclear factor E2-related factor 2 (Nrf2), and the in-vitro activation of Foxp3+ Tregs leads to an escalated expression of Nrf2. Notably, CD4-specific Nrf2 deletion intensified the allergic asthma symptoms and reduced the in-vitro iTreg differentiation. Meanwhile, DMF failed to exert protective effects on OVA-induced allergic asthma in CD4-specific Nrf2 knock-out mice. Overall, our study illustrates that DMF enhances Nrf2 signaling in T cells to assist the differentiation of Tregs, which could improve the anti-inflammatory immune response in allergic asthma.

Additional chemotherapy improves survival in stage II-III pulmonary sarcomatoid carcinoma patients undergoing surgery: a propensity scoring matching analysis.

BACKGROUND: The role of additional chemotherapy in pulmonary sarcomatoid carcinoma (PSC) is controversial. This study aimed to investigate the function of chemotherapy in PSC patients with surgical resection. METHODS: PSC patient information between 2004 to 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. X-tile software was used to calculate the optimal cut-off value to divide groups. The disease stages were recalculated according to the American Joint Commission on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging system. Propensity score matching (PSM) analysis was conducted to balance the baseline of patients. Kaplan-Meier analysis and Cox proportional hazards analysis were used to evaluate survival outcome. RESULTS: A total of 865 PSC patients were included in our study. Among them, 611 patients were only operated with surgery, and the 254 others were treated with additional chemotherapy. The median age was 69.0 years (interquartile range, 61.6 to 76.3 years). Kaplan-Meier analysis showed that patients with additional chemotherapy had longer overall survival (OS) and cancer-specific survival (CSS, P<0.05). The median OS and the 1-, 3-, 5-year OS rates were 36.0 months (95% CI: 20.5-51.5 months), 72.7%, 49.6% and 38.5% in the chemotherapy group and 29.0 months (95% CI: 23.6-34.4 months), 63.2%, 44.5% and 37.6% in the non-chemotherapy group, respectively. The OS advantage of chemotherapy was not statistically significant after PSM analysis. Moreover, Cox proportional hazards model showed that chemotherapy was an independent prognosis factor for better OS and CSS. In subgroup of stages II and III, the chemotherapy group had a survival advantage (P<0.05). Patients with young age, female gender, low histology grade, large tumor size and lobectomy surgical resection benefited more from chemotherapy. CONCLUSIONS: Chemotherapy is recommended for stages II and III PSC patients undergoing surgery, especially for those with young age, female gender, low histology grade, large tumor size and lobectomy surgical resection.

The characteristic of tumor immune microenvironment in pulmonary carcinosarcoma.

Pulmonary carcinosarcoma (PCS) is a rare but aggressive neoplasm, due to late diagnosis and early metastasis. Surgery combined with radiotherapy is a standard treatment. However, PCS features an easy relapse after surgery resection and resistance to chemotherapy and radiotherapy. Tumor immune microenvironment reflects tumor immunophenotyping and affects immunotherapy efficiency. This review summarized current studies on the characteristic of tumor immune microenvironment in PCS and discussed the potential of immunotherapy combined with other regimes strategy as a candidate for treatments in PCS.

A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations.

Recent advances have demonstrated the power of small molecules in promoting cellular reprogramming. Yet, the full potential of such chemicals in cell fate manipulation and the underlying mechanisms require further characterization. Through functional screening assays, we find that mouse embryonic fibroblast cells can be induced to trans-differentiate into a wide range of somatic lineages simultaneously by treatment with a combination of four chemicals. Genomic analysis of the process indicates activation of multi-lineage modules and relaxation of epigenetic silencing programs. In addition, we identify Sox2 as an important regulator within the induced network. Single cell analysis uncovers a novel priming state that enables transition from fibroblast cells to diverse somatic lineages. Finally, we demonstrate that modification of the culture system enables directional trans-differentiation towards myocytic, glial or adipocytic lineages. Our study describes a cell fate control system that may be harnessed for regenerative medicine.