Erythropoietin (EPO) is the principal growth factor regulating the production of red blood cells. Recent studies demonstrated that exogenous EPO acts as a neuroprotectant and regulates neurogenesis. Using a genetic approach, we evaluate the roles of endogenous EPO and its classical receptor (EPOR) in mammalian neurogenesis. We demonstrate severe and identical embryonic neurogenesis defects in animals null for either the Epo or EpoR gene, suggesting that the classical EPOR is essential for EPO action during embryonic neurogenesis. Furthermore, by generating conditional EpoR knock-down animals, we demonstrate that brain-specific deletion of EpoR leads to significantly reduced cell proliferation in the subventricular zone and impaired post-stroke neurogenesis. EpoR conditional knockdown leads to a specific deficit in post-stroke neurogenesis through impaired migration of neuroblasts to the peri-infarct cortex. Our results suggest that both EPO and EPOR are essential for early embryonic neural development and that the classical EPOR is important for adult neurogenesis and for migration of regenerating neurons during post-injury recovery.

Recent studies have revealed robust metabolic changes during cell differentiation. Mitochondria, the organelles where many vital metabolic reactions occur, may play an important role. Here, we report the involvement of SIRT3-regulated mitochondrial stress in osteoblast differentiation and bone formation. In both the osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts, robust mitochondrial biogenesis and supercomplex formation were observed during differentiation, accompanied by increased ATP production and decreased mitochondrial stress. Inhibition of mitochondrial activity or an increase in mitochondrial superoxide production significantly suppressed osteoblast differentiation. During differentiation, SOD2 was specifically induced to eliminate excess mitochondrial superoxide and protein oxidation, whereas SIRT3 expression was increased to enhance SOD2 activity through deacetylation of K68. Both SOD2 and SIRT3 knockdown resulted in suppression of differentiation. Meanwhile, mice deficient in SIRT3 exhibited obvious osteopenia accompanied by osteoblast dysfunction, whereas overexpression of SOD2 or SIRT3 improved the differentiation capability of primary osteoblasts derived from SIRT3-deficient mice. These results suggest that SIRT3/SOD2 is required for regulating mitochondrial stress and plays a vital role in osteoblast differentiation and bone formation.

Zearalenone (ZEA), an estrogenic mycotoxin, is produced mainly by Fusarium fungi. Previous studies indicated that acute ZEA exposure induced oxidative stress and damage in multiple organs. Therefore, the present study was designed to investigate the adverse effects of dietary ZEA (1.1 to 3.2 mg/kg of diet) on oxidative stress and organ damage in postweaning gilts. A total of 20 gilts (Landrace × Yorkshire × Duroc) weaned at d 21 with an average BW of 10.36 ± 1.21 kg was used in the study. Gilts were housed in a temperature-controlled room, divided into 4 treatments, and fed a basal diet only (control) or basal diet supplemented with purified ZEA at a dietary concentration of 1 (ZEA1), 2 (ZEA2), or 3 (ZEA3) mg/kg of diet for 18 d ad libitum. The actual ZEA contents (analyzed) were 0, 1.1 ± 0.02, 2.0 ± 0.01, and 3.2 ± 0.02 mg/kg for control, ZEA1, ZEA2, and ZEA3, respectively. Gilts fed different amounts of dietary ZEA grew similarly with no difference (P > 0.05) in feed intake. Vulva size increased linearly over the 18 d of feeding in gilts fed diets containing 1.1 mg of ZEA/kg or greater (P < 0.001). Relative weight of genital organs, liver, and kidney increased linearly (P < 0.05) in a ZEA-dose-dependent manner. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamate transferase, urea, and creatinine (P < 0.05), and malondialdehyde concentrations in both serum and liver (P < 0.001) were also increased linearly in a ZEA-dose-dependent manner. However, spleen relative weight (P = 0.002) and activities of total superoxide dismutase and glutathione peroxidase (in both serum and liver (P < 0.05) were decreased linearly as dietary ZEA increased. Results showed that besides genital organs, the liver, kidney, and spleen may also be target tissues in young gilts fed diets containing 1.1 to 3.2 mg of ZEA/kg for 18 d. Increased key liver enzymes in the serum suggest progressive liver damage caused by feeding ZEA, and an increase in oxidative stress in gilts is another potential impact of ZEA toxicity in pigs.

By promoting mitochondrial function, eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of NAFLD.

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short‐chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs‐mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.