Chengdu University of Traditional Chinese Medicine (CDUTCM; Chinese: 成都中医药大学; pinyin: Chéngdū zhōng yīyào Dàxué) is located in Chengdu, the capital city of Sichuan province, China. It is also known as Chengdu TCM school. It is a member of Chinese state Double First Class University Plan, with Double First Class University identity identified by the Chinese Ministry of Education.
A rare iridoid featuring an unusual 3-O-8 bridged ether bond, named rotatiridoid (1), was obtained from Phlomoides rotata (Benth. ex Hook.f.) Mathiesen, along with five known analogues. Its structure was established by means of HRESIMS, 1D and 2D NMR experiments, and ECD calculations. When evaluated in LPS-stimulated RAW 264.7 macrophages, compound 1 displayed anti-inflammatory activity, suppressing the production of pro-inflammatory mediators such as NO and ROS at 7.5 μM.
Cephalomannine (CPM), a naturally occurring taxane isolated from Taxus wallichiana, exhibits broad antitumor activity against multiple solid malignancies. However, the molecular targets responsible for this anticancer activity remain poorly defined. Here, we used an integrated chemical-genomic and functional framework to elucidate the molecular basis of CPM action in triple-negative breast cancer (TNBC). High-throughput perturbational transcriptomic profiling, computational target prediction, structural molecular modeling, and biophysical validation have converged to identify vascular endothelial growth factor receptor 1 (VEGFR1) as a key molecular determinants of CPM. Functional analysis showed that CPM potently suppressed TNBC cell proliferation and migration at nanomolar concentrations and significantly inhibited tumor growth and metastatic dissemination in orthotopic xenograft models. Mechanistically, CPM selectively attenuated VEGFR1-dependent Src/(3-catenin signaling and epithelial-mesenchymal transition (EMT) programs without altering the total receptor abundance, consistent with a non-canonical, phosphorylation-dependent mode of action. Collectively, these findings establish a previously unrecognized mechanism by which CPM exerts its antitumor and antimetastatic effects in TNBC, expand the current understanding of taxane pharmacology, and provide a rational foundation for the development of VEGFR1-targeted CPM-based therapeutic strategies for aggressive treatmentrefractory breast cancers.
Background: Clinical treatment of lung adenocarcinoma often faces the challenge of multidrug resistance (MDR), a key factor leading to the failure of the chemotherapeutic drug paclitaxel (PTX). Traditional single-treatment methods are insufficient to effectively reverse complex resistance mechanisms. Therefore, developing a synergistic delivery system that simultaneously achieves precise imaging, gene silencing, and efficient chemotherapy is of great clinical significance. Objective: This study aimed to construct a multifunctional Y-shaped DNA/PTX nanoprobe (Y-DNA/PTX) to achieve synergistic silencing of ABCB1 and beta III-tubulin genes through self-assembly drug loading technology, thereby reversing drug resistance in A549 resistant cells, enhancing the chemotherapeutic effect of PTX, and enabling targeted fluorescence imaging of tumor sites. Methods: Three precisely designed single-stranded DNA (S1, S2, S3) were used to form a Y-shaped scaffold through base pairing, and PTX was loaded onto the scaffold to construct the nanoprobe. The optimal DNA-to-PTX loading ratio was determined using a UV-Vis spectrophotometer, and the morphology was characterized using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Confocal microscopy was used to observe the uptake and targeted activation imaging of the probe in A549 cells. The inhibitory effect of the probe on drug resistance-related genes was evaluated at the cellular viability, mRNA, and protein levels using MTT assay, RT-qPCR, and Western Blot, respectively. Finally, the targeted imaging ability and antitumor activity of the probe in vivo were verified using a tumor-bearing nude mouse model. Results: This study successfully prepared spherical Y-DNA/PTX nanoparticles with a particle size of approximately 100 nm and uniform distribution. Cell experiments showed that the probe could specifically recognize A549 resistant cells and significantly downregulate the mRNA and protein expression levels of ABCB1 and beta IIItubulin by releasing antisense nucleic acids. Compared with single-drug treatment, the combination group (ASABCB1@AS-TUBB3@PTX) showed the strongest cell killing effect, exhibiting a clear dose-dependent relationship. In addition, the PTX composite probe downregulates Bcl-2 and total Caspase-3 while upregulating Bax and cleaved Caspase-3, thereby significantly activating the Caspase-dependent mitochondrial apoptotic pathway and effectively reversing multidrug resistance in A549 resistant cells. Fluorescence imaging showed that the probe containing the S6 aptamer could accurately accumulate at the tumor site, reaching a peak at 1-1.5 h after injection. In vivo efficacy studies confirmed that the Y-DNA/PTX triple combination significantly inhibited tumor growth. Histological sections (H&E and IHC) showed obvious cell necrosis and decreased target protein expression in the tumor tissue.Conclusion: This study successfully constructed a self-assembling Y-DNA/PTX nanodelivery system integrating targeting, imaging, gene therapy, and chemotherapy. This system significantly enhanced the selective killing effect of PTX on drug-resistant lung adenocarcinoma by synergistically downregulating two drug resistancerelated proteins, providing a promising precision treatment strategy for overcoming multidrug resistance in tumors.
A new iridoid glycoside (1), along with two known congeners (2−3), was isolated from Lamiophlomis rotata. The structure of new findings was elucidated by comprehensive analyses, including 1D/2D NMR, HRESIMS, hydrolysis derivatization and ECD spectroscopy. Compound 1 shows an obviously anti-inflammatory potential by inhibiting the secretion of NO, iNOS, COX-2 and ROS in LPS-stimulated RAW 264.7 macrophages at the concentration of 7.5 μM.
