The tumor microenvironment (TME) plays a pivotal role in tumorigenesis and metastasis, with cancer-associated fibroblasts (CAFs) and neutrophil extracellular traps (NETs) identified as key contributors to its dynamic regulation. This review elucidates the multifaceted roles of CAFs and NETs in tumor progression and clarifies their intricate cross talk. The underlying mechanisms by which these components promote tumor growth, metastasis, and immune evasion are also discussed. Promising therapeutic strategies include both direct targeting of CAFs and inhibition of their downstream effectors. Likewise, the disruption of NET formation using DNase or peptidylarginine deiminase 4 inhibitors represents a potential avenue for anticancer therapy. In addition, the review highlights the regulatory effects of natural products and traditional Chinese medicines on CAF-tumor interactions. Despite these advances, further investigation is necessary to facilitate clinical translation. Overall, this review provides a comprehensive understanding of the TME and promote the development of innovative therapies targeting CAF-NET cross talk to improve cancer prognosis.
In acupuncture randomized controlled trials (RCTs), the proper interpretation of results requires a thorough understanding of key statistical concepts such as p-value, effect size, and the minimal clinically important difference (MCID). This paper explores the relationships among these metrics and their implications for assessing the clinical significance of acupuncture interventions. Through case studies, the paper highlights the limitations of relying solely on p-values for determining the clinical relevance of outcomes. Although statistically significant results may be reported, these studies often fail to meet the prespecified MCID, raising concerns about their real-world applicability. This paper argues that p-values must be interpreted alongside effect size and MCID to ensure that reported benefits reflect meaningful improvements for patients. By examining both short- and long-term outcomes, this analysis emphasizes the need for a holistic approach when evaluating acupuncture RCTs, ensuring that statistical findings are translated into clinically significant improvements.
Ethnopharmacological relevance: Jinhong tablet (JHT), a traditional Chinese patent medicine prepared from four Chinese medicinal materials, is highly effective in soothing the liver and relieving depression, regulating qi and promoting blood circulation, and regulating the stomach and relieving pain. It is clinically used to treat chronic superficial gastritis (CSG) with liver-stomach disharmony. However, research on its pharmacokinetics remains limited.
Aim of the study: This study aims to investigate the pharmacokinetic characteristics of JHT in normal rats and examine its pharmacokinetic differences across normal, CSG, and intestinal microbial disorder rats.
Materials and methods: The chemical composition of JHT was identified using Orbitrap, and the main components were quantitatively analyzed. A network pharmacology screening framework was established to screen the key active ingredients of JHT in treating CSG. A quantitative method was developed to measure these ingredients in rat plasma. After oral administration of JHT at different doses, the pharmacokinetics of seven ingredients was evaluated in normal rats. Pharmacokinetic differences of four major compounds were further compared among normal, CSG, and fecal microbiota transplantation (FMT) rats. Gut microbiota changes in the three groups were analyzed using high-throughput sequencing, and Spearman correlation analysis was conducted to explore the relationship between the in vivo exposure and microbial alterations.
Results: Leveraging network pharmacology analysis, we screened seven key active compounds of JHT in the treatment of CSG and conducted pharmacokinetic studies on them. In normal rats, all seven ingredients were rapidly absorbed. Tetrahydropalmatine, corydaline, costunolide, and rhamnosylvitexin showed good exposure, whereas dehydrocorydaline, allocryptopine, and palmatine hydrochloride had low exposure. Additionally, tetrahydropalmatine, corydaline, and costunolide exhibited linear pharmacokinetics between 0.7-5.6 g/kg, whereas rhamnosylvitexin and dehydrocorydaline were linear within 0.7 and 2.8 g/kg. In CSG and FMT rats, pharmacokinetic profiles changed. CSG increased the exposure and Cmax of costunolide and rhamnosylvitexin, whereas FMT enhanced the exposure of corydaline and Cmax of rhamnosylvitexin, which correlated with 20 altered gut bacterial genera.
Conclusions: JHT exhibited linear pharmacokinetic characteristics within the appropriate dose ranges, and both the CSG pathological state and intestinal microbial disorder obviously affected its absorption and metabolism. These findings provide valuable insights for the mechanism research and clinical application of JHT.
Background: The Eph/ephrin signaling system has emerged as an important regulator of oncogenic processes, yet its specific involvement in rectal adenocarcinoma (READ) pathogenesis requires further elucidation. This study employed an integrative analytical approach combining computational biology with experimental validation to characterize Eph/ephrin family members in READ, with emphasis on EFNA3.
Methods: We employed an integrative multi-omics approach combining bioinformatics analysis with experimental validation. Transcriptomic data from the Cancer Genome Atlas and Genotype-Tissue Expression were analyzed to evaluate Eph/ephrin family expression, clinical correlations, and immune infiltration patterns. Functional validation was performed using CCK-8, wound healing, transwell migration assays, and Western blotting.
Results: Our integrated multi-omics analysis identified EFNA3 as a dual-function biomarker with both prognostic and immunological relevance in READ. Specifically, EFNA3 expression was elevated in READ tissues and correlated with poor patient prognosis. Functional characterization revealed that EFNA3 contributes to an immunosuppressive tumor microenvironment, marked by reduced cytotoxic lymphocyte infiltration and downregulation of key immune checkpoints. Mechanistically, EFNA3 overexpression promoted rectal cancer cell proliferation and migration, with pathway analysis and Western blot validation implicating Phosphoinositide 3-Kinase (PI3K)/Ak strain Transforming (AKT)/Mechanistic Target of Rapamycin (mTOR) signaling activation. Furthermore, EFNA3 expression exhibited significant correlations with drug sensitivity and potential associations with traditional Chinese herbs, suggesting its broader implications in therapeutic response and alternative medicine approaches.
Conclusion: Our findings establish EFNA3 as a key regulator of READ progression, driving both tumor aggressiveness and immune evasion. These results provide a translational framework for targeting EFNA3-mediated pathways, suggesting combined PI3K/AKT/mTOR inhibition and immune modulation as a potential therapeutic strategy for aggressive READ.