Delayed or impaired wound healing is a major health issue worldwide, especially in patients with diabetes and atherosclerosis. Here we show that expression of the circular RNA circ-Amotl1 accelerated healing process in a mouse excisional wound model. Further studies showed that ectopic circ-Amotl1 increased protein levels of Stat3 and Dnmt3a. The increased Dnmt3a then methylated the promoter of microRNA miR-17, decreasing miR-17-5p levels but increasing fibronectin expression. We found that Stat3, similar to Dnmt3a and fibronectin, was a target of miR-17-5p. Decreased miR-17-5p levels would increase expression of fibronectin, Dnmt3a, and Stat3. All of these led to increased cell adhesion, migration, proliferation, survival, and wound repair. Furthermore, we found that circ-Amotl1 not only increased Stat3 expression but also facilitated Stat3 nuclear translocation. Thus, the ectopic expressed circ-Amotl1 and Stat3 were mainly translocated to nucleus. In the presence of circ-Amotl1, Stat3 interacted with Dnmt3a promoter with increased affinity, facilitating Dnmt3a transcription. Ectopic application of circ-Amotl1 accelerating wound repair may shed light on skin wound healing clinically.

Ferroptosis plays a role in several diseases such as iron overload-induced liver diseases. Manipulation of ferroptosis has been explored as a potential therapeutic strategy to treat related diseases. Numerous antioxidants have been identified to control ferroptosis but the cell-autonomous mechanisms responsible for regulating ferroptosis remain elusive. In the present study, we found that iron overload promoted ferroptosis in hepatocytes by excessively inducing HO-1 expression, which contributed to the progression of liver injury and fibrosis, accompanied by the upregulation of the FGF21 protein level in vitro and in vivo. Interestingly, both recombinant FGF21 and Fgf21 overexpression significantly protected against iron overload-induced hepatocytes mitochondria damage, liver injury and fibrosis by inhibiting ferroptosis. In contrast, the loss of FGF21 aggravated iron overload-induced ferroptosis. Notably, FGF21-induced HO-1 inhibition (via the promotion of HO-1 ubiquitination and degradation) and NRF2 activation provide a mechanistic explanation for this phenomenon. Taken together, we identified FGF21 as a novel ferroptosis suppressor. Thus, FGF21 activation may provide an effective strategy for the potential treatment of iron overload-induced ferroptosis-related diseases, such as hereditary haemochromatosis (HH).

BackgroundBeneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the reproduction of male animals are widely described in the literature. However, there is little information about the effect of n-3/n-6 PUFA ratios on male health and reproduction. The aim of this study was to investigate the effects of diets with different n-3/n-6 PUFA ratios on the reproductive performance of male rats.MethodsEighty male Sprague Dawley (SD) rats were supplemented with diets containing different n-3/n-6 PUFA ratios (0.13, 0.40, 0.85, 1.52 and 2.85) for 60 days. Half of the rats in each group were sacrificed on day 60, and the other half were chosen to mate with female mice to assess the effects of n-3/n-6 ratios on reproductive performance.ResultsSperm density and sperm motility of the 1.52 group were higher than other groups (P < .05), and the development of testis and the morphological structure of sperm in the 1.52 group were better than other groups. Furthermore, a higher litter size and birth weights of offspring were observed in the 1.52 group. Additionally, serum reproductive hormone levels were significantly affected by the n-3/n-6 ratios.ConclusionThese findings demonstrated that a balanced n-3/n-6 ratio was important in male rat reproduction. Therefore there is a necessity to determine an appropriate n-3/n-6 PUFA ratio in man and different male animals in the future.

Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases antiobesity strains such as Akkermansia muciniphila, Lactobacillus, and Bifidobacterium. In mice lacking gut microbiota, the functional role of betaine in preventing HFD-induced obesity, metabolic syndrome, and inactivation of brown adipose tissues are significantly reduced. Akkermansia muciniphila is an important regulator of betaine in improving microbiome ecology and increasing strains that produce short-chain fatty acids (SCFAs). Increasing two main members of SCFAs including acetate and butyrate can significantly regulate the levels of DNA methylation at host miR-378a promoter, thus preventing the development of obesity and glucose intolerance. However, these beneficial effects are partially abolished by Yin yang (YY1), a common target gene of the miR-378a family. Taken together, our findings demonstrate that betaine can improve obesity and associated MS via the gut microbiota-derived miR-378a/YY1 regulatory axis, and reveal a novel mechanism by which gut microbiota improve host health.

We investigated the effects of dietary supplementation with Bacillus subtilis PB6 ( B. subtilis PB6) during late gestation and lactation on sow reproductive performance, antioxidant indices, and gut microbiota. A total of 32 healthy Landrace × Yorkshire sows on d 90 of gestation were randomly assigned to 2 groups, with 16 replicates per group, receiving basal diet (CON) or the basal diet + 0.2% B. subtilis PB6, containing 4.0 × 10 8 CFU/kg of feed (BS). The litter sizes (total born) and numbers of piglets born alive were larger in the BS group ( P < 0.01), whereas the weights of piglets born alive and the piglet birth intervals were lower in the BS group ( P < 0.05). Although the litter weights and piglet bodyweights (after cross-fostering) were lower after BS treatment ( P < 0.05), the litter sizes, litter weights, lactation survival rate, and litter weight gains at weaning were higher in BS group ( P < 0.05). The concentrations of malondialdehyde (MDA) in the sow sera at parturition were lower in the BS group ( P < 0.01). The serum total antioxidant capacity (T-AOC) at parturition and the serum catalase (CAT) concentrations on d 21 of lactation were higher in the BS group ( P < 0.05). Dietary supplementation with B. subtilis PB6 ( P < 0.05) reduced the serum endotoxin concentrations in the sows and the serum cortisol concentrations of the piglets at d 14 of lactation. The α-diversity indices of microbial were higher in the CON group ( P < 0.05). At the phylum level, B. subtilis PB6 supplementation increased the relative abundances of Gemmatimonadete and Acidobacteria (both P < 0.01) and reduced those of Proteobacteria, and Actinobacteria (both P < 0.05). At the genus level, B. subtilis PB6 supplementation increased the relative abundance of Ruminococcaceae_UCG-013 cc ( P < 0.05) and reduced that of Streptococcus ( P < 0.05). This study demonstrated that adding 4.0 × 10 8 CFU/kg B. subtilis PB6 to sows’ feed during late gestation and lactation could shorten piglet birth intervals, enhance the growth performance of suckling piglets, and improve the gut health of sows during late gestation.