Tumor-associated macrophages (TAMs) occupy an important position in the tumor microenvironment (TME), they are a highly plastic heterogeneous population with complex effects on tumorigenesis and development. TAMs secrete a variety of cytokines, chemokines, and proteases, which promote the remodeling of extracellular matrix, tumor cell growth and metastasis, tumor vessel and lymphangiogenesis, and immunosuppression. TAMs with different phenotypes have different effects on tumor proliferation and metastasis. TAMs act a pivotal part in occurrence and development of tumors, and are very attractive target to inhibit tumor growth and metastasis in tumor immunotherapy. This article reviews the interrelationship between TAMs and tumor microenvironment and its related applications in tumor therapy.

As a biopharmaceutics classification system (BCS) class IV drug, breviscapine (Bre) has low solubility in water, poor chemical stability, a short biological half-life and rapid removal from plasma. This paper prepared a Bre nanosuspension (Bre-NS) by an ultrasound-assisted anti-solvent precipitation method. Characterization of Bre-NS was studied using a Box–Behnken design concerning drug concentration in DMSO, an anti-solvent-to-solvent ratio, and sonication time. Under the optimized conditions of 170 mg/mL for the drug concentration, a 1:60 solvent-to-anti-solvent ratio, and a 9 min sonication time, the particle size of Bre-NS was 303.7 ± 7.3 nm, the polydispersity index was 0.178 ± 0.015, and the zeta potential was −31.10 ± 0.26 mV. Combined with the results from differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform-infrared spectroscopy (FT-IR), the findings indicated that the crystal form and chemical structure of Bre-NS did not change during the entire process. The optimized formulation displayed good stability, increased solubility, and better in vitro release. Therefore, the results of this study can be a reference for the delivery system design of insoluble active components and effective parts in traditional Chinese medicine.

Melanoma is one of the most common malignant tumors. The anti-PD-1 antibody is used for the treatment of metastatic melanoma. Treatment success is only 35–40% and a range of immune-related adverse reactions can occur. Combination of anti-PD1 antibody therapy with other oncology therapies has been attempted. Herein, we assessed whether chlorogenic acid liposomes modified with sialic acid (CA-SAL) combined with anti-PD1 antibody treatment was efficacious as immunotherapy for melanoma. CA-SAL liposomes were prepared and characterized. In a mouse model of B16F10 tumor, mice were treated with an anti-PD1 antibody, CA-SAL, or combination of CA-SAL + anti-PD1 antibody, and compared with no treatment controls. The tumor inhibition rate, tumor-associated macrophages (TAMs) phenotype, T-cell activity, and safety were investigated. We observed a significant decrease in the proportion of M2-TAMs and CD4⁺Fop3⁺ T cells, while there was a significant increase in the proportion of M1-TAMs and CD8⁺ T cells, and in the activity of T cells, and thus in the tumor inhibition rate. No significant toxicity was observed in major organs. CA-SAL and anti-PD1 Ab combination therapy presented synergistic anti-tumor activity, which enhanced the efficacy of the PD-1 checkpoint blocker in a mouse model of melanoma. In summary, combination immunotherapy of CA-SAL and anti-PD1 Ab has broad prospects in improving the therapeutic effect of melanoma, and may provide a new strategy for clinical treatment. Graphical Abstract

This study investigated the extraction, structural characterization, and antioxidant activity of polysaccharides derived from Akebia Fruit. The ultrasonic-assisted extraction (UAE) process of polysaccharides was optimized through the application of the Box-Behnken Design (BBD) in conjunction with the genetic algorithm-back propagation (GA-BP) artificial neural network model. The experimental data showed that the GA-BP model performed better than the BBD model, and more polysaccharide components could be extracted under the process parameters predicted by this model. The GA-BP model predicted the optimal extraction parameters as follows: the extraction temperature was 65 ℃, the solid-liquid ratio was 1:50 g/mL, the extraction power was 400 W. Experimental results showed that combining UAE with GA-BP artificial neural network not only enabled efficient extraction of polysaccharides but also optimized the extraction process. After purification, AFP-1 was obtained and its characterization was conducted. Structural analysis results indicated that compound AFP-1 was a homogeneous polysaccharide with a lamellar structure and a molecular weight of 13,775 Da. The polysaccharide contained a network of pyranose rings, which were interconnected to form a complex framework. The polysaccharide was composed of a mixture of monosaccharide units, specifically arranged in a specific configuration that included mannose, ribose, glucose, galactose, and fucose. Finally, the antioxidant activity of AFP-1 was preliminarily verified through in vitro experiments. Subsequent research could systematically explore the biological activities of AFP-1, by employing both in vitro and in vivo models.

Melanoma represents an aggressive cutaneous malignancy with limited treatment options. Ginsenoside Rg3, an active component extracted from the roots of Panax ginseng, has been extensively demonstrated to possess significant anti-tumor efficacy, showing promising application potential in the treatment of various malignancies. However, the role of Rg3 in melanoma treatment and its related mechanisms have not been reported in detail. Thus, exploring and elucidating reliable molecular mechanisms is critical. This study aimed to investigate the therapeutic efficacy of ginsenoside Rg3 in melanoma and its underlying mechanisms. This research investigated the mechanism of melanoma pathogenesis using a clinical cohort database and established a corresponding disease model. By integrating transcriptomic and metabolomic approaches, we systematically explored the intrinsic molecular mechanisms by which Rg3 regulated ferroptosis in melanoma. Then, immunohistochemistry (IHC), reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), molecular docking (MD), and molecular dynamics simulation (MDS) were used for validation. The database analysis revealed that melanoma was associated with the ferroptosis pathway. In vitro experiments showed that Rg3 inhibited the proliferation of melanoma cells. The functional annotation and enrichment analysis of differentially expressed genes and metabolites based on animal transcriptome and metabolome experiments showed that Rg3 exerted therapeutic effects by regulating the glutathione metabolism pathway and ferroptosis pathway. The detection based on the reagent kit revealed significant changes in ferroptosis-related biomarkers. IHC, RT-qPCR, and WB analyses confirmed the expression patterns of ferroptosis-associated mRNAs and proteins. MD and MDS confirmed stable binding between Rg3 and p53, SLC7A11, GPX4, and FTH1 proteins. Rg3 induced melanoma ferroptosis via the p53/SLC7A11/GPX4 pathway, offering therapeutic potential for melanoma.