Fungi are an important and prolific source of secondary metabolites (SMs) with diverse chemical structures and a wide array of biological properties. In the past two decades, however, the number of new fungal SMs by traditional monoculture method had been greatly decreasing. Fortunately, a growing number of studies have shown that co-culture strategy is an effective approach to awakening silent SM biosynthetic gene clusters (BGCs) in fungal strains to produce cryptic SMs. To enrich our knowledge of this approach and better exploit fungal biosynthetic potential for new drug discovery, this review comprehensively summarizes all fungal co-culture methods and their derived new SMs as well as bioactivities on the basis of an extensive literature search and data analysis. Future perspective on fungal co-culture study, as well as its interaction mechanism, is supplied.

Cancer stem cells (CSCs) are important factors contributing to tumorigenesis. We examined whether CSCs isolated from colorectal cancer (CRC) cells possess metastatic properties that can be transferred to non‐CSCs via the delivery of miR‐200c enclosed in extracellular vesicles (EVs). The inhibitory effect of atractylenolide I (ATL‐1), a traditional Chinese medicinal compound, on miR‐200c activity and metastatic transfer was investigated. EVs were isolated from colorectal CSCs. The expression of miR‐200c was evaluated in CSCs and CSC‐derived EVs, and horizontal transfer of metastatic properties via EVs to non‐CSCs was investigated in terms of cell behavior and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling. CSCs isolated from metastatic CRC cells exhibited higher levels of miR‐200c than those in nonmetastatic CRC cells. Overexpression of miR‐200c in CSCs enhanced metastatic potential by promoting proliferation and inhibiting apoptosis, in turn leading to the release of EVs carrying an excess of miR‐200c. Non‐CSCs co‐cultured with miR‐200c‐containing EVs exhibited enhanced invasion and stemness maintenance associated with PI3K/Akt/mTOR activation, demonstrating successful metastatic transfer via EV delivery. Furthermore, ATL‐1 impaired the EV‐mediated transfer of metastatic properties by suppressing miR‐200c activity and disrupting EV uptake by non‐CSCs. EVs are critical signal transducers that facilitate intercellular communication and exchange of metastatic properties, which can be controlled by ATL‐1. The findings are useful in the development of microRNA‐based anticancer strategies by targeting EV‐mediated activity, especially using natural compounds.

Allergic asthma is a common respiratory inflammation disease. The crude Radix Paeoniae Alba (RPA) and its processed products have been used frequently as antipyretic and anti-inflammatory agents in traditional medicine. To evaluate the effect of honey and bran processing, different fractions of RPA were used for treating anti-allergic asthma in the ovalbumin (OVA)-induced mice model, and then, the most effective fraction of RPA and stir-frying Radix Paeoniae Alba with honey and bran (FRPA) for treating anti-allergic asthma were compared mutually for pharmacological effects. The results showed that the treatment of the dichloromethane fraction of RPA significantly improved the pathological condition of lung tissues, decreased the number of eosinophils and other cells in bronchoalveolar lavage fluid (BALF), and the increased the expression of various inflammatory factors. Furthermore, the study discovered that the lung pathological conditions, compared with the high dose of dichloromethane RPA fraction, could be ameliorated by high dose of dichloromethane FRPA fraction treatment. Moreover, the expression of inflammatory factors and the phosphorylation of the PI3K/AKT signaling pathway could be diminished by FRPA. Finally, the contents of compounds with a significant difference in the FRPA dichloromethane fraction were paeoniflorin, ethyl gallate, pentagalloylglucose, galloylpaeoniflorin, and others by UPLC/Q-TOF-MS analysis. These findings suggest that the dichloromethane fraction of FRPA has an enhancement effect on anti-allergic asthma and provide the experimental basis for exploring the processed mechanism of RPA.

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