Background: The application of apatinib is immensely limited by its acquired drug resistance. This research investigates whether cordycepin, a component from Cordyceps could synergize with apatinib to improve its anticancer effect on non-small cell lung cancer (NSCLC) cells. Methods: The NSCLC cell lines A549, PC9, and H1993, and human bronchial epithelial (HBE) cell line Bears-2B were used in this study. Cell counting kit 8, colony formation assays, wound healing assay, transwell assay, and flow cytometry analysis were performed to assess the cell viability, the migration ability, and invasion ability of the cells. Kyoto encyclopedia of genes and genomes (KEGG), western blotting and molecular docking was applied to analyze the possible pathways affected by cordycepin. Results: The combination of cordycepin and apatinib in a ratio of 5:1 synergistically reduced proliferation of NSCLC cells, inhibited cell migration and invasion, increased cell apoptosis by altering cell cycle in NSCLC A549 and PC9 cells. The VEGF/PI3K/Akt pathway was inhibited after treatment with cordycepin and apatinib. Conclusion: Our findings demonstrated that the combination of cordycepin and apatinib has synergistically anticancer effect on NSCLC cells by down-regulating VEGF/PI3K/Akt signaling pathway. This result indicated that cordycepin and apatinib could be a promising drug combination against NSCLC.

Graphical Ginsenoside Rg3 promotes cell growth through activation of mTORC1 and increasing mitochondrial biogenesis.

Background. Inflammatory bowel disease (IBD) is becoming a global disease. A percentage of IBD patients will not react to therapy or will lose their response. Qu-Yu-Jie-Du Decoction (QYJD) is a traditional Chinese medicine formula commonly used for intestinal diseases. It has been reported that QYJD has an anti-inflammatory effect, but the mechanism is not fully understood. In this study, we mainly evaluated the anti-inflammatory effect of QYJD and explored the possible mechanisms. Methods. Twenty-four BALB/c mice were randomly divided into 4 groups according to their body weight, namely, the control group, the dextran sulfate sodium (DSS) group, the DSS+QYJD group, and the QYJD group. Mice were given 3 DSS drinking water freely, and at the same time, mice were given normal saline or QYJD (4.44mg/g/d), respectively. Mental state, faeces, and weight were recorded every day. On the 10th day, the mice were sacrificed and collected for investigation. The length of the mice colon was measured. Histological analysis was used to detect the morphological changes in the colon. Immunohistochemistry was used to measure the infiltration of macrophages (F4/80, CD163) and neutrophils (Ly6G). Colorimetry was used to detect the myeloperoxidase (MPO) activity of colon tissues. ELISA was utilized to detect associated inflammatory cytokines and chemokines in colon tissues. Results. QYJD alleviated the weight loss and colitis symptoms of mice caused by DSS. QYJD fought against the shortening of the intestine caused by DSS; that is, it improved the decline of intestinal compliance in mice and had a protective effect on colon tissues. The mechanisms were related to downregulating macrophages and neutrophils in colon tissues of infiltration. Besides, QYJD simultaneously reduced the activity of myeloperoxidase activity (MPO) and the contents of IL-1β, IL-6, TNF-α, TGF-β, CCL2, and CXCL2 in colon tissues. Conclusions. QYJD can ameliorate DSS-induced colitis in mice and the mechanism is connected with a reduction in neutrophil and macrophage infiltration.

While cancer-associated fibroblasts (CAFs) significantly influence tumor progression, their temporal dynamics remain poorly understood. We investigated time-dependent interactions between non-small cell lung cancer (NSCLC) cells and CAFs, and evaluated rosmarinic acid (RA)’s potential to modulate these interactions. HCC827 lung adenocarcinoma cells and MRC-5 fibroblasts were co-cultured in vitro. CAF activation markers (α-SMA, FAP) and epithelial-mesenchymal transition (EMT) were assessed through morphological and molecular analyses. Xenograft models with different tumor-to-fibroblast ratios (1:1, 1:2) evaluated tumor growth dynamics and RA’s therapeutic effects combined with gefitinib. Time-course analysis revealed a biphasic pattern in tumor-CAF interactions. CAF activation markers reached peak levels by day 6, followed by maximal EMT marker expression in NSCLC cells at day 8. In xenograft models, higher CAF proportions initially inhibited tumor growth but accelerated tumor progression. RA treatment significantly attenuated CAF activation markers and reversed EMT-related changes in cancer cells, leading to reduced tumor growth in CAF-enriched xenografts. The combination of RA with gefitinib demonstrated enhanced anti-tumor effects compared to gefitinib alone. CAFs exhibit temporally biphasic roles in NSCLC progression characterized by initial suppression followed by promotion of tumor microenvironment deterioration. RA effectively modulates these tumor-stromal interactions, enhances gefitinib efficacy, and delays the development of drug resistance.

Background: This study investigated the expression and role of Synaptosome associated protein 25 (SNAP25) in high-grade neuroendocrine carcinoma (HGNEC).Methods: We used differentially expressed analysis and weighted gene co-expression network analysis (WGCNA) to identify key genes and modules in HGNEC. KEGG and GO analyses helped understand these genes’ roles, and ROC curves assessed their diagnostic value. We also studied SNAP25’s relation to immune infiltration and confirmed findings with in vitro and vivo experiments and datasets.Results: WGCNA identified 595 key genes related to pathways like MAPK signaling, GABAergic synapse, and cancer-related transcriptional misregulation. Top genes included SNAP25, MYC, NRXN1, GAD2, and SYT1. SNAP25 was notably associated with M2 macrophage infiltration. Dataset GSE40275 confirmed SNAP25’s high expression and poor prognosis in HGNEC. qRT-PCR and WB analyses showed increased SNAP25 and c-MYC levels in HGNEC, promoting MEK/ERK pathway activity. Reducing SNAP25 decreased H1299 cell proliferation, migration, invasion, and levels of c-MYC, MEK, and ERK. Finally, in vivo experiments further confirmed that SNAP25 knockout can inhibit tumor growth.Conclusion: SNAP25 regulates c-MYC activation by stimulating the MEK/ERK pathway, ultimately influencing the development of HGNEC.