Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer.

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.

Response of tree growth to nutrient addition is size dependent in a subtropical forest.

Understanding how nutrient addition affects the tree growth is critical for assessing forest ecosystem function and processes, especially in the context of increased nitrogen (N) and phosphorus (P) deposition. Subtropical forests are often considered N-rich and P-poor ecosystems, but few existing studies follow the traditional "P limitation" paradigm, possibly due to differences in nutrient requirements among trees of different size classes. We conducted a three-year fertilization experiment with four treatments (Control, N-treatment, P-treatment, and NP-treatment). We measured soil nutrient availability, leaf stoichiometry, and relative growth rate (RGR) of trees across three size classes (small, medium and large) in 64 plots. We found that N and NP-treatments increased the RGR of large trees. P-treatment increased the RGR of small trees. RGR was mainly affected by N addition, the total effect of P addition was only 10 % of that of N addition. The effect of nutrient addition on RGR was mainly regulated by leaf stoichiometry. This study reveals that nutrient limitation is size dependent, indicating that continuous unbalanced N and P deposition will inhibit the growth of small trees and increase the instability of subtropical forest stand structure, but may improve the carbon sink function of large trees.

Bioactive phenyl ether derivatives from the marine-derived fungus Aspergillus carneus.

A new phenyl ether derivative, 3-hydroxy-5-(3-hydroxy-5-methylphenoxy)-4-methoxybenzoic acid (1), along with two known analogues, 3,4-dihydroxy-5-(3-hydroxy-5-methylphenoxy)benzoic acid (2) and 3-hydroxy-5-(3-hydroxy-5-methylphenoxy)benzoic acid (3), were isolated from the fungus Aspergillus carneus collected from South China Sea. The structure elucidation of 1 was determined based on extensive NMR and MS spectroscopic analyses. Compound 2 showed a strong antioxidant activity with an IC50 value of 19.3 µM which was close to the positive control ascorbic acid (IC50 = 15.3 µM).