Effects of food quantity on the ingestion and egestion of MPs with different colors by Daphnia magna.

Aquatic organism uptake and accumulate microplastics (MPs) through various pathways, with ingestion alongside food being one of the primary routes. However, the impact of food concentration on the accumulation of different types of MPs, particularly across various colors, remains largely unexplored. To address this gap, we selected Daphnia magna as a model organism to study the ingestion/egestion kinetics and the preference for different MP colors under varying concentrations of Chlorella vulgaris. Our findings revealed that as the concentration of Chlorella increased, the ingestion of MPs by D. magna initially increased and then showed a decline. During the egestion phase within clean medium without further food supply, an increase in food concentration during the ingestion phase led to a slower rate of MP discharge; while when food was present during the egestion phase, the discharge rate accelerated for all treatments, indicating the importance of food ingestion/digestion process on the MPs bioaccumulation. Furthermore, in the presence of phytoplankton, D. magna demonstrated a preference for ingesting green-colored MPs, especially at low and medium level Chlorella supply, possibly due to the enhanced food searching activities. Beyond gut passage, we also examined the attachment of MPs to the organism's body surface, finding that the number of adhered MPs increased with increasing food concentration, likely due to the intensified filtering current during food ingestion. In summary, this study demonstrated that under aquatic environment with increasing phytoplankton concentrations, the ingestion and egestion rates, color preferences, as well as surface adherence of MPs to filter feeding zooplanktons will be significantly influenced, which may further pose ecological risks. Our results offer novel insights into the unintentional accumulation of MPs by zooplankton, highlighting the complex interactions between food availability and MPs accumulation dynamics.

EGFR mediates epithelial­mesenchymal transition through the Akt/GSK-3ß/Snail signaling pathway to promote liver cancer proliferation and migration.

Epidermal growth factor receptor (EGFR) is expressed in various types of cancer and is associated with the malignant biological behavior of cancer cells. In the present study, the expression of EGFR in hepatocellular carcinoma (HCC) tissues and liver cancer cells was detected by immunohistochemical staining, western blotting and immunofluorescence. Furthermore, a lentivirus was transduced into HepG2 liver cancer cells to knock down EGFR expression. Cell proliferation and migration, and the expression levels of epithelial-mesenchymal transition (EMT) markers were assessed by EdU staining, Cell Counting Kit-8, colony formation, wound healing and Transwell assays, and western blotting. The results revealed that EGF/EGFR can mediate EMT through the Akt/glycogen synthase kinase-3ß (GSK-3ß)/Snail signaling pathway to promote HepG2 cell proliferation and migration. Inhibition of the activation of the EGFR signaling pathway can help to partially reverse the EMT phenotype, and inhibit the proliferation and migration of HepG2 cells. In conclusion, the EGFR/Akt/GSK-3ß/Snail signaling pathway serves an important role in HCC progression, and inhibition of the activation of the EGFR signaling pathway may be a valuable strategy in liver cancer treatment.

Evaluation of the inhibitory effect of azoles on pharmacokinetics of lenvatinib in rats both in vivo and in vitro by UPLC-MS/MS.

BACKGROUND: Lenvatinib is a multitargeted tyrosine kinase inhibitor used in the treatment of a variety of solid tumors. This study aims to investigate the potential pharmacokinetic interactions between lenvatinib and various azoles (ketoconazole, voriconazole, isavuconazole and posaconazole) when orally administered to rats. METHODS: A total of 30 Sprague-Dawley rats were randomly allocated into five groups and administered 20 mg/kg of ketoconazole, voriconazole, isavuconazole and 30 mg/kg of posaconazole and 0.5% CMC-Na, through gavage for a duration of 7 days prior to the commencement of the experiment. On the final day, the rats were given 10 mg/kg of lenvatinib. The blood concentration of lenvatinib was determined using UPLC-MS-MS. In vitro lenvatinib were incubated with azoles and rat liver microsomes (RLMs) or human liver microsomes (HLMs). Molecular docking was lastly used to examine the binding strength of the enzymes and ligands with Autodock Vina. RESULTS: AUC and Cmax of lenvatinib significantly increased with each of the azoles (p < 0.05), whereas CLz/F decreased 0.83-flod, 0.41-fold (p < 0.05) and 0.72-fold (p < 0.01) in voriconazole, isavuconazole and ketoconazole in rats. The IC50 of lenvatinib with the azoles were 0.237, 1.300, 0.355 and 2.403 µM in RLMs and 0.160, 1.933, 3.622 and 1.831 µM in HLMs. Molecular docking analysis suggested that azoles exhibited a strong binding ability towards the target enzymes. CONCLUSION: It is imperative to acknowledge the potential drug-drug interactions mediated by CYP3A4 between azoles and lenvatinib, as these interactions hold significant implications for their clinical utilization.

Alternative splicing events and function in the tumor microenvironment: New opportunities and challenges.

Alternative splicing controls gene expression at the transcriptional level, producing structurally and functionally distinct protein heterodimers. Aberrant alternative splicing greatly affects cell development and plays an important role in the invasion and metastasis of many types of cancer. Recently, it has been shown that alternative splicing can alter the tumor microenvironment and regulate processes such as remodeling, immunity, and inflammation in the tumor microenvironment. However, there is no comprehensive literature review of the complex relationship between alternative splicing and the tumor microenvironment. Therefore, this review aims to collect all the latest data on this topic and provide a new perspective on the therapeutic and potential prognostic markers of cancer.

Molecular interplay between EIF4 family and circular RNAs in cancer: Mechanisms and therapeutics.

The eukaryotic translation initiation factor 4 (EIF4) family is a major contributor to the recruitment of mRNAs to ribosomes during the initial translation stage in eukaryotes, whose dysregulation either allows for cancer transformation or prevents disordered cancerous cell growth. Circular RNAs (circRNAs), which exhibit distinctive structures and are widely expressed in eukaryotes, are anticipated to be clinical diagnostic biomarkers for cancer therapy. There is considerable evidence that EIF4s can influence the biogenesis, transport, and function of circRNAs and, in turn, circRNAs can control the expressions of EIF4s through certain molecular pathways. Herein, we primarily review the emerging studies of the EIF4 family and pinpoint the roles of dysregulated EIF4s in cancer. We also evaluate the patterns of intricate interactions between circRNAs and EIF4s and discuss the potential utility of circRNA-based therapeutics targeting EIF4s in clinical cancer research.

Tanshinone IIA ameliorates diabetic cardiomyopathy by inhibiting Grp78 and CHOP expression in STZ-induced diabetes rats.

Diabetic cardiomyopathy (DCM), one of the common diabetic complications, causes a high rate of mortality in patients with diabetes. Tanshinone IIA (TSIIA), one of the components of Salvia miltiorrhiza (Danshen), has anti-oxidative stress activity and is widely used to treat diabetes-associated diseases. However, its efficacy on DCM remains unclear. The present study aimed to investigate the potential therapeutic function of TSIIA on DCM in an experimental diabetic rat model. Streptozotocin (STZ)-induced diabetic rats were intraperitoneally injected with TSIIA for 6 weeks. The present results indicated that blood glucose concentration was slightly reduced in the low-dose TSIIA treatment group. TSIIA injection was also noted to improve cardiac function, and restore loss of mitochondrial cristae, swollen mitochondrial matrix and disorganized myofibrils in myocardial cells, which are thought to be characteristics of apoptosis. Furthermore, TSIIA injection could increase the activity of superoxide dismutase in STZ-induced diabetic rats, and suppress the endoplasmic reticulum (ER) stress signaling pathway via reducing the expression of glucose-regulated protein 78 and C/EBP homologous protein. These results provide evidence that TSIIA may ameliorate DCM in diabetic rats, possibly via suppressing oxidative stress and ER stress activation.