The relatively higher temperature of the tumor site and the temperature responsive shape transition of pNIPAM hydrogel make the controllable drug release possible for oncotherapy.

Context: CD4 + CD25+ regulatory T (Treg) lymphocytes are critical for immune homeostasis. Foxp3 (Forkhead Box protein P3) is always considered as a marker of function and identities determination of Treg cells because of special occurring in Treg cell. People who lack Treg cells or have a low expression of Foxp3 gene will suffer fatal autoimmunity. Scientists are trying to use Treg cells as a treatment for autoimmune disease, such as systemic lupus erythematosus. Objective: Our objective was to induce Foxp3 + CD4+ T cells from naïve CD4 + T cells isolated from C57 mice spleen in vitro using stimuli that include the short chain fatty acid sodium butyrate. Furthermore, to explore the relationship between Foxp3+ T cells induction and epigenetic modification, by observing the changes of Foxp3, Ezh2 (Enhancer of Zeste Homolog 2) and phosphorylated Ezh2 in the induced Treg cells. Materials and methods: The naïve CD4+ T cells were separated from C57 mice spleen by immunomagnetic separation. Anti-CD28, anti-CD3, IL-2, TGF-β1, and sodium butyrate were added with proper concentration to induce Foxp3 expression during 72 hours. Then, we observed the effect of GSK126 (Ezh2 inhibitor) on the induction within the same over 72 hours duration. Then, western blot and Q-PCR were used to see the changes in gene/protein expression of Foxp3, Ezh2, and phosphorylated Ezh2. Results: According to our results, group 3 that received full stimulus had a significant higher level of Foxp3 and Ezh2 expression (p < .05, comparing with group 1,2) and adding 5 mM sodium butyrate to the full stimulus (group 5) increased significantly the induction of Foxp3 and Ezh2 than control group and higher concentration group (p < .05, comparing with group 3,4, 6). The gene and protein expression of Foxp3 and Ezh2 both were enhanced in group 5 (p < .05 comparing with group 3). However, phosphorylated Ezh2 decreased in group 5 (p < .05 comparing with group3). Sodium butyrate removed part inhibition of GSK126, result in Foxp3 and Ezh2 expression (p < .05, p < .01, comparing with group7). Conclusion: In this study, we were able to transform CD4 + T cells into CD4 + Foxp3 + T cell by using stimulus like antibodies (anti-CD28, anti-CD3) and cytokines (IL-2, TGF-β1). Sodium butyrate contributes to CD4 + Foxp3 + T cell induction in vitro and at an optimum concentration of 5 mM. Sodium butyrate promotes expression of Ezh2 and Fxop3 of T cells in vitro; in addition, to lowering relative expression of phosphorylated Ezh2 probably be influencing some pathways like PI3K-Akt. Epigenetic modification is also thought to take essential part into the upregulation of Foxp3 from naïve CD4 + Tcells.

Background and Aim: As one of the second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare EGFR mutations. This study aimed to compare the effectiveness and safety of 30 and 40 mg of afatinib in patients with non–small cell lung cancer (NSCLC) using qualitative and quantitative analysis methods so as to provide reference for clinical medication.Methods: The PubMed, Embase, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were thoroughly searched from inception to February 26, 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality. RevMan and Stata 15.0 were used for meta-analysis.Results: Twelve cohort studies including 1290 patients for final analysis were selected; of which, 1129 patients were analyzed to measure the effectiveness outcomes and 470 patients were analyzed for safety outcomes. In patients with non-brain metastasis, the progression-free survival of the first- or second-line treatment with reduced-dose afatinib was equivalent to the conventional dose. In terms of safety, the reduced dose could significantly lower the incidence of severe diarrhea and severe rash, but not the total incidence of diarrhea, rash, and all levels of paronychia.Conclusions: The incidence of common serious adverse reactions was significantly lower with 30 mg of afatinib than with 40 mg of afatinib in patients with NSCLC. The effectiveness appeared to be similar to that in patients with non-brain metastasis. This study provides a reference for clinical dose reduction of afatinib.Systematic Review Registration: [PROSPERO], identifier [CRD42021238043]