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.

High-efficiency triplet-triplet annihilation upconversion microemulsion with facile preparation and decent air tolerance.

Current research of triplet-triplet annihilation upconversion (TTA-UC) faces difficulty such as overuse of organic solvents and quenching of excited triplet sensitizers by molecular oxygen. Herein, we propose an efficient and facile preparation strategy of TTA-UC microemulsion to overcome these issues. With simple device and short preparation process, air-stable TTA-UC with a high upconversion efficiency of 16.52% was achieved in microemulsion coassembled from TritonX114, tetrahydrofuran and upconverting chromophores (platinum octaethyl-porphyrin and 9,10-diphenylanthracene). This is comparable to the highest UC efficiency ever reported for TTA-UC microemulsion systems. The excellent UC performance of TX114-THF could be attributed to two perspectives. Firstly, small-size micelle accommodated chromophores up to high concentrations in organic phase, which promoted efficient molecular collision. Additionally, high absorbance at 532 nm ensured full use of excitation light, getting more long wavelength photons involved in the TTA-UC process. Moreover, air-stable TTA-UC also performed well in microemulsion with various surfactants, including nonionic surfactants (Tween 20, Tween 80, Triton X-110, Triton X-114), ionic surfactants (sodium dodecyl sulfate, cetyltrimethyl ammonium bromide) and block copolymers (pluronic F127, pluronic P123), through three conjectural assembly models according to the structural characteristics of surfactant molecules (concentrated, uncompacted and scattered). These discoveries could provide estimable reference for selection of surfactants in relevant fields of TTA-UC.

A novel dual polarization multiplexing RoF system integrating optical fiber and FSO channel with AMI downlink signals.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

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.