[Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-ß Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia].

OBJECTIVE: To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-ß on T cell acute lymphoblastic leukemia (T-ALL) cell lines. METHODS: Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy. RESULTS: Different concentrations of FA-2-b-ß significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-ß inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-ß reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/ß-catenin inhibitor (ICG001), the process was further intensified. CONCLUSION: Agaricus Blazei Extract FA-2-b-ß inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.

Synthesis, characterization and biological activity of novel copper complexes containing a ß-carboline derivative and amino acids.

Copper complexes have long been considered as a promising class of anticancer or antibacterial therapeutics. In this paper, two novel copper(II) complexes containing a ß-carboline derivative and amino acids, namely [Cu(1-Im-ßc)(L-Val)]ClO4·0.5H2O (Cu1) and [Cu(1-Im-ßc)(L-Phe)]ClO4·0.5H2O (Cu2), where 1-Im-ßc = 1-(2-imidazolyl)-ß-carboline, L-Val = L-valine, and L-Phe = L-phenylalanine, were designed and synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, molar conductivity measurements, and mass spectrometry to determine their spatial structures and compositions. Both complexes bind to DNA by insertion. The complexes also show a good affinity for human serum albumin (HSA). In addition, the antitumor activity of the two complexes against lung cancer cells (A549), cervical cancer cells (HeLa), and breast cancer cells (MBA-MD-231) is significantly superior to that of the traditional antitumor drug, cisplatin. Finally, the anticancer mechanism results show that the complexes can induce apoptosis in HeLa cells, which is associated with mitochondrial damage, oxidative stress caused by reactive oxygen species (ROS) production, and activation of the caspase protein family. This study demonstrates that the introduction of aromatic heterocyclic alkaloid ligands with a broad spectrum of biological activities and water-soluble amino acid ligands into copper complexes can regulate their amphiphilic properties and biological activity, so as to obtain highly efficient copper-based therapeutics.

[Microbial Community Succession in Industrial Composting with Livestock Manure and Peach Branches and Relations with Environmental Factors].

This study sets out to understand the evolution of the microbial community structure in industrial composting with livestock manure and peach branches. Pig manure, peach branches, and decomposed organic fertilizer were used as materials for composting. Changes in physical and chemical indicators and the evolution in the structure of the compost microbial community, determined by high-throughput sequencing, were analyzed. The results of physical and chemical parameters show that the pile reached the high-temperature stage on day 2, and the thermophilic period lasted for 30 days. The changes in total carbon were volatile, and there was an overall decline in the amount of TOC in the whole process of composting; The final content of TN was 20.58 g·kg-1, which was 5.90% lower compared to the initial compost. Alpha analysis indicated that a different microbial community diversity existed at different times during aerobic composting periods. At the bacterial phyla level, Firmicutes and Actinobacteria were the dominant phyla, and the proportion of relative abundance were 79.31%-95.09% and 2.98%-19.70%, respectively, in the entire compost. The relative abundance of Firmicutes and Actinobacteria were 87.36% and 9.66%, respectively, and their respective relative abundances were 79.38% and 19.70% at the end of composting. At the bacterial genus level, the dominant group changed from Clostridium_sensu_stricto_1, Terrisporobacter, and Bacillus to norank_f_Bacillaceae, Bacillus, Oceanbacillus, and Pseudogracilibacillus; Regarding the fungus phyla, the Ascomycota was the dominant phylum. For the fungus genus, the relative abundance of norank_c_Sordariomycetes gradually increased during composting, and finally was predominant group. The redundancy analysis (RDA) showed that the correlation rank between environmental factors and microbial community structure was:pH > NH4+-N > T > TOC > TN, where pH had the greatest impact on the microbial community composition. norank_c_Sordariomycetes, norank_o_Sordariales, and norank_c_Agaricomycetes may be related to the volatilization of ammonium nitrogen.