Tumor-derived extracellular vesicles delivering TNF-α promotes colorectal cancer metastasis via the NF-kB/LAMB3/AKT axis by targeting SNAP23.

Accumulating evidence have demonstrated that cytokines are enriched in tumor-derived extracellular vesicles (EVs) and widely involved in tumorigenesis of various types of carcinomas, including colorectal cancer (CRC). Nevertheless, the functions of cytokines in EVs secreted from colorectal cancer cells remain largely unknown. In the present study, we found that TNF-α was elevated in EVs from CRC patient serum samples and CRC cell lines, of which the expression was associated with aggressive features of colorectal cancer. EV TNF-α secretion is dependent on synaptosome-associated protein 23 (SNAP23). Functional experiments revealed that EV TNF-α promotes CRC cell metastasis via the NF-κB pathway by targeting SNAP23. Mechanistically, SNAP23 was transcriptionally upregulated by EV TNF-α/NF-κB axis to enhance the expression of laminin subunit beta-3 (LAMB3), thereby activating the PI3K/AKT signaling pathway and consequently facilitate CRC progression. Based on our findings, we could conclude that EV TNF-α plays an oncogenic role in CRC progression through SNAP23, which in turn promotes EV TNF-α secretion, suggesting that EV TNF-α/SNAP23 axis may serve as a diagnostic biomarker and potential therapeutic target for CRC.

To Save Pangolins: A Nutritional Perspective.

Pangolins are one of the world's most trafficked mammals. Since pangolins are highly adapted to ants and termites, they are important for controlling forest termite infestations. In addition to their ecological value, pangolins have economic and medicinal value. Currently, poaching and habitat destruction have radically reduced the number of pangolins, and Manis pentadactyla, Manis javanica, and Manis culionensis are now considered the most threatened pangolin species. In addition to the control of hunting and illegal trade, ex situ breeding is also a useful conservation method. However, many technical obstacles still limit the success of ex situ pangolin breeding. The special feeding traits of pangolins require a diet that meets nutritional and ethological needs. Based on the existing literature and practical experience, this review aims to compare the natural diet and successful diet in the human care of pangolins, to outline the key factors of successful ex situ maintenance from a dietary perspective, and the strategies to improve their conservation success in animal care centers and in the wild. The type of food used in successful pangolin protection agencies is quite variable in nutritional composition. In the diet of pangolins in the wild, the nutrient profile of different species of termites and ants and even the same species of termites and ants but different types (queens, soldiers, etc.) also displays differences. The crude protein content of some ants is higher than that of other foods, such as eggs, milk, and common cat food. The mineral and vitamin concentrations of ants also exceed many common food items, such as oil, meat, and eggs. However, not much is known about the bioavailability of minerals from ants and termites. Based on comparisons between foods, it is clear that the main difference between diets in the wild and in human care of pangolins is that the latter contains fewer insects and vitamins, such as vitamin E, vitamin A, and vitamin B2, and more carbohydrates and non-protein substances than the former. Although many successful dietary formulae have been developed, the pangolin's nutritional needs are still less well studied. A diet with the nutrient concentrations observed in the wild may add to successful ex situ conservation.