Serum Iron Overload Activates the SMAD Pathway and Hepcidin Expression of Hepatocytes via SMURF1.

Background and Aims: Liver iron overload can induce hepatic expression of bone morphogenic protein (BMP) 6 and activate the BMP/SMAD pathway. However, serum iron overload can also activate SMAD but does not induce BMP6 expression. Therefore, the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain unclear. This study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD pathway. Methods: A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin (Holo-Tf). A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 days. Western blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of hepcidin. Results: Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to BMP6. The E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression; specifically, SMURF1 expression dramatically decreased when the serum iron concentration was increased. Additionally, the expression of SMURF1 substrates, which are important molecules involved in the transduction of BMP/SMAD signaling, was significantly upregulated. Furthermore, in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron overload. Conclusions: SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.

Polysaccharides as Potential Anti-tumor Biomacromolecules -A Review.

Cancer, as one of the most life-threatening diseases, has attracted the attention of researchers to develop drugs with minimal side effects. The bioactive macromolecules, such as the polysaccharides, are considered the potential candidates against cancer due to their anti-tumor activities and non-toxic characteristics. The present review provides an overview on polysaccharides' extraction, isolation, purification, mechanisms for their anti-tumor activities, structure-activity relationships, absorption and metabolism of polysaccharides, and the applications of polysaccharides in anti-tumor therapy. Numerous research showed extraction methods of polysaccharides had a significant influence on their activities. Additionally, the anti-tumor activities of the polysaccharides are closely related to their structure, while molecular modification and high bioavailability may enhance the anti-tumor activity. Moreover, most of the polysaccharides exerted an anti-tumor activity mainly through the cell cycle arrest, anti-angiogenesis, apoptosis, and immunomodulation mechanisms. Also, recommendations were made to utilize the polysaccharides against cancer.