Antitumor activity of dictamnine against colorectal cancer through induction of ferroptosis and inhibition of M2 macrophage polarization via the MAPK signaling.

Colorectal cancer (CRC) is an aggressive cancer type globally. Surgery and chemotherapy are often ineffective at curing CRC. Dictamnine is a natural product derived from Dictamnus dasycarpus Turcz. root bark and possesses multi-pharmacological properties, including anticancer effects. Nevertheless, the biological roles and the possible mechanism of dictamnine in CRC are still unclear. Here, we demonstrated that dictamnine blocked cell viability and proliferation in DLD-1 human colorectal adenocarcinoma cells and LoVo human colon cancer cells. Dictamnine triggered CRC cell ferroptosis, as evidenced by enhanced levels of reactive oxygen species, malondialdehyde, and Fe2+ levels, alongside downregulation of glutathione peroxidase 4 protein expression. In addition, CD163 (HPA ID: HPA046404) was highly expressed and CD68 (HPA ID: CAB000051) was lowly expressed in CRC tissues and CRC cell culture medium-cultured THP-1 monocytes-derived macrophages. The patients with CD163 low-expression lived much longer than those with CD163 high-expression, indicating that M2 polarization of macrophages was related to poor prognosis of CRC. Dictamnine markedly inhibited CD163 protein expression, transforming growth factor-ß and arginase 1 mRNA expressions and IL-10 production in macrophages with CRC cell co-culture, suggesting that dictamnine impeded M2 polarization of macrophages. Mechanistically, dictamnine repressed ERK phosphorylation in CRC cells. The treatment with the ERK activator tBHQ counteracted the effects of dictamnine on CRC cell proliferation and ferroptosis, as well as its inhibitory effect on M2 polarization of macrophages. Results of a xenograft model showed that dictamnine effectively hindered CRC tumor growth in vivo. Collectively, these data provide evidence for the clinical trials of dictamnine as a novel drug for CRC therapy.

The Growth Inhibition of Polyethylene Nanoplastics on the Bait-Microalgae Isochrysis galbana Based on the Transcriptome Analysis.

The adverse effects of microplastics on microalgae species have been extensively studied, but their impact on the bait microalgae entering the food chain has not been well understood. This study investigated the cytological and physiological response of Isochrysis galbana to polyethylene microplastics (PE-MPs, 10 µm) and nanoplastics (PE-NPs, 50 nm). The results showed that PE-MPs had no significant impact on I. galbana, while PsE-NPs obviously inhibited cell growth, reduced chlorophyll content, and caused a decline in carotenoids and soluble protein. These changes in the quality of I. galbana could negatively affect its use as aquaculture feed. To understand the molecular response mechanism of I. galbana to PE-NPs, transcriptome sequencing was performed. The result revealed that the TCA cycle, purine metabolism, and some key amino acid syntheses were down-regulated by PE-NPs, while the Calvin cycle and fatty acid metabolism were up-regulated to tolerate PE-NP pressure. Microbial analysis showed that the bacterial community structure associated with I. galbana was significantly altered at the species level by PE-NPs. In conclusion, this study provides new insights into the physiological stress response caused by microplastic pollution based on transcriptome and bacterial community analysis. The findings highlight the need to mitigate the release of microplastics into the environment to prevent their harmful effects on aquatic ecosystems and will be helpful in understanding the impact of polyethylene nanoplastics on the bait microalgae.

Biogeography and Adaptive evolution of Streptomyces Strains from saline environments.

The genus Streptomyces is a widespread genus within the phylum Actinobacteria and has been isolated from various environments worldwide. However, little is known about whether biogeography affects distributional pattern of Streptomyces in salty environments. Such information is essential for understanding the ecology of Streptomyces. Here we analyzed four house-keeping genes (16S rRNA, rpoB, recA and atpD) and salty-tolerance related genes (ectA-ectD) of 38 Streptomyces strains isolated from saline environments in Yunnan and Xinjiang Provinces of western China. The obtained Streptomyces strains were classified into three operational taxonomic units, each comprising habitat-specific geno- and ecotype STs. In combination with expressional variations of salty-tolerance related genes, the statistical analyses showed that spatial distance and environmental factors substantially influenced Streptomyces distribution in saline environments: the former had stronger influence at large spatial scales (>700 km), whereas the latter was influential at large (>700 km) and small spatial scales (<700 km). Plus, the quantitative analyses of salty-tolerence related genes (ectA-D) indicated that Streptomyces strains from salt lakes have higher expression of ectA-D genes and could accumulate larger quantities of ectoine and hydroxyectoine than strains from salt mines, which could help them resist to salinity in the hypersaline environments.