Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes of cell death and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, and iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation and iron overload. Recent reports have shown that ferroptosis at the cellular and organism levels can prevent an inflammatory storm and cancer development. Emerging evidence suggests potential mechanisms (e.g., system Xc-, glutathione peroxidase 4 (GPX4), lipid peroxidation, glutathione (GSH), and iron chelators) are involved in ferroptosis, which may mediate biological processes such as oxidative stress and iron overload to treat cancer. To date, there are at least three pathways that mediate ferroptosis in cancer cells: system Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, and ATG5/ATG7/NCOA4. Here, we summarize recent advances in the occurrence and development of ferroptosis in the context of cancer, the associations between ferroptosis and various modulators, and the potential mechanisms and therapeutic strategies targeting ferroptosis for the treatment of cancer.

Fusarium infection with concurrent production of deoxynivalenol (DON) causes an increasing safety concern with feed worldwide. This study was conducted to determine the effects of varying levels of DON in diets on growth performance, serum biochemical profile, jejunal morphology, and the differential expression of nutrients transporter genes in growing pigs. A total of twenty-four 60-day-old healthy growing pigs (initial body weight = 16.3 ± 1.5 kg SE) were individually housed and randomly assigned to receive one of four diets containing 0, 3, 6 or 12 mg DON/kg feed for 21 days. Differences were observed between control and the 12 mg/kg DON treatment group with regards to average daily gain (ADG), although the value for average daily feed intake (ADFI) in the 3 mg/kg DON treatment group was slightly higher than that in control (P<0.01). The relative liver weight in the 12 mg/kg DON treatment group was significantly greater than that in the control (P<0.01), but there were no significant differences in other organs. With regard to serum biochemistry, the values of blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate amino transferase (AST) in the 3 treatment groups were higher than those in the control, and the serum concentrations of L-valine, glycine, L-serine, and L-glutamine were significantly reduced in the 3 treatment groups, especially in the 12 mg/kg DON group (P<0.01). Serum total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) were markedly decreased after exposure to DON contaminated feeds (P<0.01). The villi height was markedly decreased and the lymphocyte cell numbers markedly increased in the 3 DON contaminated feeds (P<0.01). The mRNA expression levels of excitatory amino acid transporter-3 (EAAC-3), sodium-glucose transporter-1 (SGLT-1), dipeptide transporter-1 (PepT-1), cationic amino acid transporter-1 (CAT-1) and y+L-type amino acid transporter-1 (LAT-1) in control were slightly or markedly higher than those in the 3 DON treatment groups. These results showed that feeds containing DON cause a wide range of effects in a dose-dependent manner. Such effects includes weight loss, live injury and oxidation stress, and malabsorption of nutrients as a result of selective regulation of nutrient transporter genes such as EAAC-3, SGLT-1, PepT-1, CAT-1 and LAT-1.

Diarrheal disease is a common health problem with complex causality. Although diarrhea is accompanied by disturbances in microbial diversity, how gut microbes are involved in the occurrence of diarrhea remains largely unknown. Here, using a pig model of post-weaning stress-induced diarrhea, we aim to elucidate and enrich the mechanistic basis of diarrhea. We found significant alterations in fecal microbiome, their metabolites, and microRNAs levels in piglets with diarrhea. Specifically, loss of ssc-miRNA-425-5p and ssc-miRNA-423-3p, which inhibit the gene expression of fumarate reductase (frd) in Prevotella genus, caused succinate accumulation in piglets, which resulted in diarrhea. Single-cell RNA sequencing indicated impaired epithelial function and increased immune response in the colon of piglet with diarrhea. Notably, the accumulated succinate increased colonic fluid secretion by regulating transepithelial Cl-secretion in the epithelial cells. Meanwhile, succinate promoted colonic inflammatory responses by activating MyD88-dependent TLR4 signaling in the macrophages. Overall, our findings expand the mechanistic basis of diarrhea and suggest that colonic accumulation of microbiota-produced succinate caused by loss of miRNAs leads to diarrhea in weanling piglets.

Oxidative stress commonly occurs in pig production, which can severely damage the intestinal function of weaned piglets. This study was conducted to investigate the effects of D-galactose with different levels used to induce chronic oxidative stress on growth performance, intestinal morphology and gut microbiota in weaned piglets. The results showed that addition of 10 and 20 g/kg BW D-galactose reduced average daily gain and average daily feed intake from the first to the third week. 10 g/kg BW D-galactose increased the concentration of serum MDA at the second and third week. 10 g/kg BW D-galactose significantly influenced the jejunal and ileal expressions of GPx1, CAT1, and MnSOD. The results of 16S rRNA sequencing showed that compared with the control, 10 and 20 g/kg BW D-galactose significantly decreased the relative abundance of Tenericutes, Erysipelotrichia, Erysipelotrichales, and Erysipelotrichaceae, while increased the relative abundance of Negativicutes, Selenomonnadales, and Veillonellaceae. The results indicated that treatment with 10 g/kg BW/day D-galactose for 3 weeks could induce chronic oxidative stress, reduce the growth performance and alter gut microbiota in weaned piglets.