Immunometabolism in bladder cancer microenvironment

The initiation and progression of bladder cancer (BC), is dependent on its tumor microenvironment (TME). On the other hand, cancer cells shape and train TME to support their development, respond to treatment and migration in an organism. Immune cells exert key roles in the BC microenvironment and have complex interactions with BC cells. These complicated interplays result in metabolic competition in the TME leading to nutrient deprivation, acidosis, hypoxia and metabolite accumulation, which impair immune cell function. Recent studies have demonstrated that immune cells functions are closely correlated with their metabolism. Immunometabolism describes the functional metabolic alterations that take place within immune cells and the role of these cells in directing metabolism and immune response in tissues or diseases such as cancer. Some molecules and their metabolites in the TME including glucose, fatty acids and amino acids can regulate the phenotype, function and metabolism of immune cells. Hence, here we describe some recent advances in immunometabolism and relate them to BC progression. A profound understanding of the metabolic reprogramming of BC cells and immune cells in the TME will offer novel opportunities for targeted therapies in future.

Plant Triterpenoids Regulate Endophyte Community to Promote Medicinal Plant Schisandra sphenanthera Growth and Metabolites Accumulation

Beneficial interactions between endophytes and plants are critical for plant growth and metabolite accumulation. Nevertheless, the secondary metabolites controlling the feedback between the host plant and the endophytic microbial community remain elusive in medicinal plants. In this report, we demonstrate that plant-derived triterpenoids predominantly promote the growth of endophytic bacteria and fungi, which in turn promote host plant growth and secondary metabolite productions. From culturable bacterial and fungal microbial strains isolated from the medicinal plant Schisandra sphenanthera, through triterpenoid-mediated screens, we constructed six synthetic communities (SynComs). By using a binary interaction method in plates, we revealed that triterpenoid-promoted bacterial and fungal strains (TPB and TPF) played more positive roles in the microbial community. The functional screening of representative strains suggested that TPB and TPF provide more beneficial abilities to the host. Moreover, pot experiments in a sterilized system further demonstrated that TPB and TPF play important roles in host growth and metabolite accumulation. In summary, these experiments revealed a role of triterpenoids in endophytic microbiome assembly and indicated a strategy for constructing SynComs on the basis of the screening of secondary metabolites, in which bacteria and fungi join forces to promote plant health. These findings may open new avenues towards the breeding of high yielding and high metabolite-accumulating medicinal plants by exploiting their interaction with beneficial endophytes.

ABA accelerates blackberry (Rubus spp.) fruit ripening by positively affecting ripening-related gene expression and metabolite profiles

BACKGROUND: The softness of blackberry fruits limits their postharvest shelf-life and commercial use, and abscisic acid (ABA) is considered one of the key hormones involved in fruit ripening. OBJECTIVE: This study aimed to explore the underlying physiological and molecular actions of ABA on blackberry fruit ripening and softening. METHODS: Various physiological indices of and plant hormone levels in treated and untreated blackberry fruits were determined simultaneously. The differentially expressed genes (DEGs) were analyzed by RNA-sequencing, and their expression profiles were detected. The ripening mechanism was elucidated by UHPLC-MS using two groups of fruits at 28 d. RESULTS: After 25 d, the ABA concentration and polygalacturonase (PG) and beta-1,4-endoglucanase (EG) activities in ABA-treated fruits were significantly higher than those in untreated fruits. Large differences in the expression profiles were detected at 28 d. The expression of DEGs related to cell wall softening and ABA synthesis was largely triggered after 25 or 28 d. Sixty-nine differentially accumulated metabolites were ultimately annotated as related to fruit ripening. CONCLUSIONS: ABA stimulates blackberry fruit ripening by promoting cell wall enzyme activities, the expression of various ripening-related genes and metabolite accumulation.