Effects of exogenous spermidine on autophagy and antioxidant capacity in ovaries and granulosa cells of Sichuan white geese.

Autophagy can inhibit ovarian senescence induced by oxidative stress and regulate follicle development and atresia, but its mechanism is still unclear. Exogenous spermidine can induce autophagy and scavenge reactive oxygen species (ROS). In this experiment, oxidative stress in Sichuan white geese ovaries and follicular granulosa cells (GCs) was caused by 3-nitropropionic acid (3-NPA) and spermidine was added to explore the effect of exogenous spermidine inducing autophagy and inhibiting oxidative stress in vivo and in vitro. Research results showed that putrescine, spermidine and spermine contents in goose ovaries in the group treated with spermidine combined with 3-NPA were 2.70, 1.94, and 1.70 times higher than those in the group treated with 3-NPA, respectively (P < 0.05). The contents of spermidine and spermine in GCs were 1.37 and 0.89 times higher in the spermidine in combination with the 3-NPA group than in the 3-NPA group, respectively (P < 0.05). LC3 and p62 were mainly expressed in the follicular granulosa layer. The LC3-II/I ratio and p62 level in GCs in the spermidine combined with 3-NPA treatment group were 1.37 and 0.77 times higher than that of the 3-NPA treatment group, respectively (P < 0.05). 3-NPA treatment significantly increased ROS level and the apoptosis rate in GCs, while the combined treatment of spermidine and 3-NPA reversed this change (P < 0.05). In conclusion, spermidine alleviated the oxidative damage induced by 3-NPA by improving the antioxidant capacity of ovaries and follicular GCs of Sichuan white geese and may be alleviated by inducing autophagy in GCs.

This study investigated the effects of exogenous spermidine on oxidative stress induced by 3-nitropropionic acid (3-NPA) in ovaries and granulosa cells of Sichuan white geese. In ovarian tissue, spermidine can reduce malondialdehyde accumulation induced by 3-NPA by increasing antioxidant enzyme activity, thus alleviating the oxidative damage induced by 3-NPA. In addition, spermidine can also improve the morphological structure of follicles and alleviate the structural damage caused by 3-NPA. Our results showed that autophagy-associated proteins are mainly concentrated in the granulosa layer of follicles and spermidine can alter their expression. Subsequently, we found that spermidine could induce autophagy and reduce the accumulation of reactive oxygen species and apoptosis rate induced by 3-NPA in granulosa cells. Therefore, we speculate that spermidine can alleviate oxidative stress induced by 3-NPA by inducing autophagy in granulosa cells. In conclusion, spermidine can relieve oxidative stress induced by 3-NPA by increasing the activity of antioxidant enzymes, and may also relieve oxidative stress by inducing autophagy.

SARS-CoV-2 continuously optimizes its codon usage to adapt to human lung environment.

Viruses need to utilize the resources from host cells to reproduce themselves. RNA translation rate, which is largely determined by codon usage, is the rate-limiting step across the life cycle of viruses. Adapting to the codon usage of hosts would help virus better proliferate. We retrieved the time-course mutation profile of millions of world-wide SARS-CoV-2 sequences. For synonymous mutations, we defined whether a mutation elevate or reduce the relative synonymous codon usage (RSCU). We found that if a synonymous mutation in SARS-CoV-2 increases the RSCU (calculated from human lungs), denoted as delta RSCU > 0, then this mutation is positively selected because the allele frequency (AF) of this mutation increases with time, and vice versa. The results suggest that in SARS-CoV-2, the synonymous mutations that increase codon optimality are beneficial to the virus and are favored by natural selection. For the first time, we used the dynamics of allele frequency to demonstrate that SARS-CoV-2 is continuously optimizing its codon usage to adapt to human lungs. Nevertheless, adaptation to other human tissues cannot be excluded. These results warn us that under this global pandemic, synonymous mutations in SARS-CoV-2 should not be automatically ignored since they indeed change the fitness of the virus.

Didymin ameliorates dexamethasone-induced non-alcoholic fatty liver disease by inhibiting TLR4/NF-κB and PI3K/Akt pathways in C57BL/6J mice.

The present study aimed to investigate the protective effects and mechanisms of Didymin from Mentha spicata on non-alcoholic fatty liver disease (NAFLD) induced by dexamethasone and high-fat diet (DEX/HFD) in C57BL/6J mice. Briefly, mice were acclimated for 5 days and then subjected to DEX/HFD from days 5 to 28; meanwhile, the animals were treated with Didymin or Silibinin from days 12 to 28. Key indicators of NAFLD were then detected, including the pathological changes of liver tissues, serum biochemical indicators, inflammation, oxidative stress, apoptosis and lipid metabolism. Besides, the expressions of pivotal genes and proteins of the TLR4/NF-κB and PI3K/Akt pathways were examined to further elucidate the mechanisms of Didymin. The results demonstrated that Didymin significantly extenuated hepatocyte damage and lipid disorder. Moreover, Didymin markedly decreased hepatocyte apoptosis by regulating the expressions of B-cell lymphoma-2 (Bcl-2) family and the expressions of the caspase family. Further study elucidated that Didymin decreased the expressions of toll-like receptor 4 (TLR4), as well as the phosphorylation of inhibitor of nuclear factor kappa-B (IκB) and nuclear factor kappa-B p65 (NF-κB p65), suggesting the inhibition of Didymin on the TLR4/NF-κB pathway. Similarly, the PI3K/Akt pathway was also inhibited by Didymin, as evidenced by the decrease in the phosphorylation levels of PI3K and Akt. In summary, this study indicates that Didymin mitigates NAFLD by alleviating lipidosis and suppressing the TLR4/NF-κB and PI3K/Akt pathways, which may be a potential natural medicine for the treatment of NAFLD.