Biological Procedures Online最新文献

Background & objective: Weitiao No. 3 decoction (WD-3), a clinically used adjuvant therapy for advanced gastrointestinal tumors, lacks clarified mechanisms in gastric cancer (GC).

Methods: We profiled chemical constituents by liquid chromatography-mass spectrometry (LC-MS), predicted putative targets and pathways via network pharmacology, evaluated binding by molecular docking, and validated pharmacological effects in MGC-803 cells and mouse xenograft models.

Results: LC-MS identified 344 constituents; network analyses yielded 188 putative targets and highlighted core nodes (e.g., AKT1, EGFR, PIK3CA, PPARG). Pathway enrichment and docking converged on the PPARγ (PPARG)/AMPK axis. Experimentally, WD-3 suppressed proliferation and migration, induced G1-phase arrest, and increased PPARγ and phospho-AMPK; perturbation of PPARγ modulated AMPK activation and anti-tumor effects. In vivo, high-dose WD-3 reduced xenograft tumor growth in a dose-dependent manner without overt hepato-renal histopathologic toxicity.

Conclusions: Using LC-MS, network pharmacology, docking, and in vitro/in vivo assays, we found that WD-3 suppresses GC cell proliferation/migration and xenograft growth, accompanied by increased total PPARγ and AMPK Thr172 phosphorylation, supporting involvement of the PPARγ/AMPK axis.

Background: There are notable challenges in the development of effective therapeutic interventions for primary liver cancer (PLC). The role of ribosomal protein (RP) RPL29 in cancer has been rarely reported and the underlying mechanisms of RPL29 in the progression of Hepatocellular carcinoma (HCC) remain unclear.

Methods: In the present study, the expression level and prognostic value of RPL29 in patients with HCC was evaluated by bioinformatics and immunohistochemistry. Moreover, gene expression was suppressed using targeted siRNAs and enhanced through plasmids containing specific gene cDNA sequences. Subsequently, assessments of cell viability and invasive capacity were conducted. Additionally, Western blot analyses and subcutaneous xenograft models in nude mice were utilized to elucidate the potential function of RPL29 in regulating the malignant phenotype of HCC.

Results: The expression of RPL29 was found to be significantly elevated in HCC tissues. Further investigation demonstrated that RPL29 actively promotes the proliferation and metastatic potential of HCC cells. Moreover, RPL29 was shown to enhance the expression of Exosome Component 4 (EXOSC4), thereby contributing to the progression and metastasis of HCC. Both RPL29 and EXOSC4 were markedly overexpressed in HCC tissues and were associated with poorer overall survival and disease-free survival outcomes. Notably, the overexpression of RPL29 was able to restore cell viability and invasive capabilities in HCC cells in EXOSC4 silenced cells. In addition, we conducted a screening of two small molecule drugs that specifically target EXOSC4.

Conclusion: The present study demonstrated that RPL29 facilitates HCC progression by regulating the expression of EXOSC4, which provides a novel therapeutic option for patients with HCC.

Background: With the successive listing of immune checkpoint inhibitors in China, a new era of immunotherapy for malignant tumors has opened. However, this study has several limitations. Xianglian granule (XG), a Chinese herbal formula, has been proven to have a therapeutic effect on tumors in animal experiments. Our aim was to evaluate the efficacy and safety of XG combined with programmed death ligand 1 (PD-1) in pancancer patients through a randomized, double-blind, controlled trial.

Methods: Patients with cancer who received PD-1 monoclonal antibody therapy were randomized to the XG or control group according to the blinded method for 9 weeks. The primary endpoint was the overall survival (OS) rate, and the secondary endpoint was the incidence rate of immune-related adverse events (irAEs). Related biological markers were observed.

Results: A total of 91 patients were included in the study. The 3-year OS rates of the XG group and the control group were 35.56% and 15.22%, respectively (P = 0.0012). The lactate dehydrogenase (LDH) level in the XG group was lower than that in the other groups, especially in the lung cancer patients (P = 0.06, P = 0.03). The two groups showed similar safety. The incidence rate of irAEs was 22.2% in the XG group and 32.6% in the control group (P = 0.27). In addition, XG can reduce D-lactic acid (D-LA) and diamine oxidase (DAO) contents (P = 0.012, P < 0.001). The B lymphocyte count and percentage of the XG group increased (P = 0.04, P = 0.035), and the interleukin-2 level decreased (P = 0.045). The Cox regression results suggested that the potential factors of the prognostic model might be XG treatment, D-LA and B lymphocyte count (P = 0.002, P < 0.001, P = 0.001).

Conclusion: XG had efficacy-enhancing and toxicity-reducing effects on pancancer patients when combined with a PD-1 monoclonal antibody. The mechanisms may be related to the participation of the intestinal barrier, B lymphocytes and interleukin-2. D-LA and B lymphocytes may be potential factors in the prognostic model of pancancer patients treated with immunotherapy.

Hepatocellular carcinoma (HCC) ranks among the most prevalent malignant tumors worldwide, exhibiting persistently high incidence and mortality rates. Metabolic reprogramming, particularly the 'Warburg effect' characterized by aberrantly enhanced glycolysis, serves as a hallmark feature of HCC and various other malignancies. Even under oxygen-sufficient conditions, tumor cells preferentially utilize the glycolytic pathway to convert glucose into lactate. This metabolic mode not only supplies essential energy (ATP) for rapid tumor cell proliferation but, more critically, provides key intermediate metabolites for synthesizing macromolecules such as nucleic acids, lipids, and amino acids. It concurrently regulates the pH and redox status of the tumor microenvironment, thereby robustly supporting tumor growth, invasion, and metastasis. Recent years have witnessed significant advances in research on glycolytic regulatory mechanisms in HCC, revealing an exceptionally complex regulatory network composed of diverse molecules and signaling pathways. This review aims to systematically organize and elucidate the multi-layered molecular mechanisms regulating glycolytic reprogramming in HCC. We will comprehensively examine the multidimensional regulation of key enzymes and glucose transporters within the glycolytic pathway, encompassing transcriptional control, post-translational modifications, and other regulatory layers; We will conduct an in-depth analysis of the central role played by non-coding RNAs (ncRNAs)-including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs)-within the glycolytic regulatory network of HCC; Elucidate how classical signaling pathways and key transcription factors synergistically interact to precisely regulate the glycolytic process; Analyze how post-translational modifications fine-tune the activity of glycolytic enzymes; And discuss how various components within the tumor microenvironment and intercellular communication mechanisms reshape the metabolic phenotypes of HCC. Furthermore, this review summarizes the clinical application value of positron emission tomography (PET) technology based on glycolytic activity in the diagnosis, staging, and prognostic evaluation of HCC. Through a comprehensive elucidation of these complex regulatory networks, this work aims to enhance comprehension of HCC metabolic characteristics and provide a theoretical foundation for exploring novel therapeutic targets and clinical strategies.