Paeonol alleviates ulcerative colitis by modulating PPAR-γ and nuclear factor-κB activation.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease affecting the gastrointestinal tract. Although paeonol has been used for treating UC due to its anti-inflammatory and antioxidant effects, the underlying mechanisms remain unclear. In this study, we investigated the mechanisms of paeonol's action on UC by conducting in-vitro and in-vivo studies using NCM460 cells and RAW264.7 cells, and the DSS-induced mice colitis model. The in vitro studies demonstrate that paeonol exerts inhibitory effects on the activation of the NF-κB signaling pathway through upregulating PPARγ expression, thereby attenuating pro-inflammatory cytokine production, reducing reactive oxygen species levels, and promoting M2 macrophage polarization. These effects are significantly abrogated upon addition of the PPARγ inhibitor GW9662. Moreover, UC mice treated with paeonol showed increased PPARγ expression, which reduced inflammation and apoptosis to maintain intestinal epithelial barrier integrity. In conclusion, our findings suggest that paeonol inhibits the NF-κB signaling pathway by activating PPARγ, reducing inflammation and oxidative stress and improving Dss-induced colitis. This study provides a new insight into the mechanism of treating UC by paeonol.

Fe3O4@R837 Nanoplatform Enhances Chemical Dynamic Therapy and Immunotherapy: Integrated Transcriptomic Analysis Reveals Key Genes in Breast Cancer Prognosis.

Breast cancer represents a substantial contributor to mortality rates among women with cancer. Chemical dynamic therapy is a promising anticancer strategy that utilizes the Fenton reaction to transform naturally occurring hydrogen peroxide (H2O2) into hydroxyl radicals (•OH). Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells. In this study, we proposed a Fe3O4@R837 smart nanoplatform that can trigger the Fenton reaction and induce immune responses in breast cancer treatment. Furthermore, we performed transcriptome sequencing on breast cancer samples and used the R package (limma) to analyze differential expression profiles and select differentially expressed genes (DEGs). We obtained clinical information and RNA expression matrix data from The Cancer Genome Atlas database to perform survival analysis and identify prognostic-related genes (PRGs) and molecular subtypes with distinct prognoses. We used the TIMER 2.0 web and other methods to determine the tumor immune microenvironment and immune status of different prognostic subtypes. We identified DPGs by taking the intersection of DEGs and PRGs and performed functional analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to elucidate potential mechanisms. Subsequently, we constructed a protein-protein interaction network using the STRING database to visualize the interactions between the DPGs. We screened hub genes from the DPGs using the Cytoscape plugin and identified six hub genes: CD3E, GZMK, CD27, SH2D1A, ZAP70, and TIGIT. Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.

Acute inflammatory reaction during anti-angiogenesis therapy combined with immunotherapy as a possible indicator of the therapeutic effect: Three case reports and literature review.

The posterior line treatment of unresectable advanced or metastatic gastrointestinal (GI) tumors has always been a challenging point. In particular, for patients with microsatellite stable (MSS)/mismatch repair proficient (pMMR) 0GI tumors, the difficulty of treatment is exacerbated due to their insensitivity to immune drugs. Accordingly, finding a new comprehensive therapy to improve the treatment effect is urgent. In this study, we report the treatment histories of three patients with MSS/pMMR GI tumors who achieved satisfactory effects by using a comprehensive treatment regimen of apatinib combined with camrelizumab and TAS-102 after the failure of first- or second-line regimens. The specific contents of the treatment plan were as follows: apatinib (500 mg/d) was administered orally for 10 days, followed by camrelizumab (200 mg, ivgtt, day 1, 14 days/cycle) and TAS-102 (20 mg, oral, days 1-21, 28 days/cycle). Apatinib (500 mg/d) was maintained during treatment. Subsequently, we discuss the possible mechanism of this combination and review the relevant literature, and introduce clinical trials on anti-angiogenesis therapy combined with immunotherapy.

NPM1 promotes cell proliferation by targeting PRDX6 in colorectal cancer.

Colorectal cancer is a malignant tumor that begins in the colorectal mucosal epithelium. NPM1 is a nucleolar phosphoprotein that has been linked to tumor progression in humans. NPM1 is significantly overexpressed in a variety of tumors, including colorectal cancer, but its role and mechanism in colorectal cancer remain unknown. Therefore, the purpose of this study was to discover the role of NPM1 in promoting colorectal cancer proliferation via PRDX6 and its molecular mechanism. NPM1 knockdown or overexpression inhibited or promoted the proliferation and cell cycle progression of HCT-116 and HT-29 colorectal cancer cells, respectively, according to our findings. Furthermore, NPM1 knockdown or overexpression increased or decreased intracellular ROS levels. Animal experiments revealed that NPM1 knockdown or overexpression inhibited or promoted the growth of colorectal cancer cells transplanted subcutaneously. NPM1 knockdown or overexpression reduced or increased PRDX6 expression and related enzyme activities, respectively, according to our findings. NPM1 formed a complex with CBX3 as evidenced by immunoprecipitation, and the double luciferase reporter gene assay confirmed that the CBX3-NPM1 complex promoted PRDX6 transcription. Our data support the role of NPM1 in promoting the proliferation of colorectal cancer, which may be accomplished by CBX3 promoting the expression of the antioxidant protein PRDX6 and thus inhibiting intracellular ROS levels. NPM1 and PRDX6 are potential colorectal cancer therapeutic targets.

Application method affects pesticide efficiency and effectiveness in wheat fields.

BACKGROUND: There is an urgent need to enhance pesticide effectiveness while reducing adverse environmental impacts, based on the pesticide reduction program that requires net zero growth in chemical pesticide applications by 2020. Agricultural production can benefit from appropriate pesticide application using the optimal method. In this study, the effects of different application methods on the effectiveness, spray deposition, and residue behaviour of 48% phenamacril · tebuconazole suspension concentrate (SC) in wheat production were compared to determine the most efficient and effective method. RESULTS: 48% phenamacril · tebuconazole SC was most effective in controlling Fusarium head blight (FHB) and mycotoxin contamination. Statistically significant differences in the control effect, spray deposition, initial residues, and half-life (t1/2 ) were subsequently observed with different application methods, suggesting that the application method plays a key role in pesticide availability and control efficiency. The differences in control efficiency and pesticide residues between application methods were thought to be related to droplet size, droplet distribution, and penetrability. Unmanned aerial vehicle and mister sprayers were found to effectively increase the control efficacy of 48% phenamacril · tebuconazole SC in terms of FHB control and mycotoxin concentrations, as well as enhancing pesticide availability. CONCLUSION: These findings are of theoretical and practical value for the scientific application of pesticides in wheat, helping to enhance pesticide utilization while reducing harmful residues. © 2019 Society of Chemical Industry.

Quantitative Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry Method for Comparison of Prochloraz Residue on Garlic Sprouts after Soaking and Spraying Treatment.

Prochloraz is a fungicide that is widely used on vegetables to maintain freshness during storage. To ensure that prochloraz is used in a safe way that reduces the levels of residue on the product, we evaluated two treatment methods (soaking and spraying) that are commonly used for garlic sprouts. An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for prochloraz residue on garlic sprouts. The linear range of the method was 5⁻500 µg/kg and the correlation coefficient was 0.9983. The average recovery range was 88⁻94%, and the relative standard deviation range was 2.6⁻9.7%. Garlic sprout samples that had been soaked in or sprayed with prochloraz were collected from cold storage facilities in Laixi and Pingdu, China. For the soaked samples, the ranges for the levels of prochloraz residue on the whole garlic sprouts and stems (edible portion) were 15.76⁻25.14 mg/kg and 0.58⁻1.62 mg/kg, respectively. For the sprayed samples, the ranges for the levels of prochloraz residue on the whole garlic sprouts and stems were 1.85⁻7.89 mg/kg and 0.01⁻1.29 mg/kg, respectively. The results of this study provide a scientific basis for rationalizing the use of prochloraz and improving the safety of edible garlic sprouts.

Residue Dynamics and Risk Assessment of Prochloraz and Its Metabolite 2,4,6-Trichlorophenol in Apple.

The residue dynamics and risk assessment of prochloraz and its metabolite 2,4,6-trichlorophenol (2,4,6-TCP) in apple under different treatment concentrations were investigated using a GC-ECD method. The derivatization percent of prochloraz to 2,4,6-TCP was stable and complete. The recoveries of prochloraz and 2,4,6-TCP were 82.9%-114.4%, and the coefficients of variation (CV) were 0.7%-8.6% for the whole fruit, apple pulp, and apple peel samples. Under the application of 2 °C 2.0 g/L, 2 °C 1.0 g/L, 20 °C 2.0 g/L, and 20 °C 1.0 g/L treatment, the half-life for the degradation of prochloraz was 57.8-86.6 d in the whole fruit and apple peel, and the prochloraz concentration in the apple pulp increased gradually until a peak (0.72 mg·kg-1) was reached. The concentration of 2,4,6-TCP was below 0.1 mg·kg-1 in four treatment conditions and not detected (