Autophagy, originally found in liver experiments, is a cellular process that degrades damaged organelle or protein aggregation. This process frees cells from various stress states is a cell survival mechanism under stress stimulation. It is now known that dysregulation of autophagy can cause many liver diseases. Therefore, how to properly regulate autophagy is the key to the treatment of liver injury. mechanistic target of rapamycin (mTOR)is the core hub regulating autophagy, which is subject to different upstream signaling pathways to regulate autophagy. This review summarizes three upstream pathways of mTOR: the phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) signaling pathway, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, and the rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-extracellular activated protein kinase kinase (MEK)/ extracellular-signal-regulated kinase (ERK) signaling pathway, specifically explored their role in liver fibrosis, hepatitis B, non-alcoholic fatty liver, liver cancer, hepatic ischemia reperfusion and other liver diseases through the regulation of mTOR-mediated autophagy. Moreover, we also analyzed the crosstalk between these three pathways, aiming to find new targets for the treatment of human liver disease based on autophagy.

Although significant advances have been made in synthetic nerve conduits and surgical techniques, complete regeneration following peripheral nerve injury (PNI) remains far from optimized. The repair of PNI is a highly heterogeneous process involving changes in Schwann cell phenotypes, the activation of macrophages, and the reconstruction of the vascular network. At present, the efficacy of MSC-based therapeutic strategies for PNI can be attributed to paracrine secretion. Exosomes, as a product of paracrine secretion, are considered to be an important regulatory mediator. Furthermore, accumulating evidence has demonstrated that exosomes from mesenchymal stem cells (MSCs) can shuttle bioactive components (proteins, lipids, mRNA, miRNA, lncRNA, circRNA, and DNA) that participate in almost all of the abovementioned processes. Thus, MSC exosomes may represent a novel therapeutic tool for PNI. In this review, we discuss the current understanding of MSC exosomes related to peripheral nerve repair and provide insights for developing a cell-free MSC therapeutic strategy for PNI.

Zearalenone (ZEA) is one of the common mycotoxins in feeds. ZEA and its metabolites have estrogen-like activity and can competitively bind to estrogen receptors, causing reproductive dysfunction and damage to reproductive organs. The toxicity mechanism of ZEA mainly inhibits the antioxidant pathway and antioxidant enzyme activity, induces cell cycle arrest and DNA damage, and blocks the process of cellular autophagy to produce toxic effects. In animal husbandry practice, when animals ingest ZEA-contaminated feed, it is likely to lead to abortion in females, abnormal sperm viability in males with inflammatory reactions in various organs, and cancerous changes in the reproductive organs of humans when they ingest contaminated animal products. In this paper, we reviewed in detail how ZEA induces oxidative damage by inducing the generation of reactive oxygen species (ROS) and regulating the expression of genes related to oxidative pathways, induces germ cell apoptosis through the mitochondrial and death receptor pathways, and activates the expression of genes related to autophagy in order to induce cellular autophagy. In addition, the molecular detoxification mechanism of ZEA is also explored in this paper, aiming to provide a new direction and theoretical basis for the development of new ZEA detoxification methods to better reduce the global pollution and harm caused by ZEA.

The aim of this study was to investigate the role of selenomethionine (SeMet) in alleviating AFB1 induced intestinal injury by inhibiting intestinal oxidative stress. Forty 35-day-old rabbits were divided randomly into 4 groups (control group, AFB1 group, 0.2 mg/kg Se + AFB1 group, 0.4 mg/kg Se + AFB1 group). From the first day of the experiment, the two treatment groups were fed 0.2 mg/kg SeMet or 0.4 mg/kg SeMet daily for 21 days. On the 17th day, all rabbits in the model group and the two treatment groups were given intragastric AFB1 daily for 5 days. The ADG, ADFI and FCR of the rabbits were examined. Rabbit jejunum tissue was collected for hematoxylin- eosin staining (HE), PCNA detection, immunofluorescence and WB. Intestinal tissue IL-1β, IL-6 and TNF-α were examined by enzyme-linked immunosorbent assay (ELISA). The results showed that the production performance was decreased, the levels of ROS and MDA were increased in intestinal tissues, the activity of antioxidant enzymes was decreased and the expression levels of Nrf2 and HO-1 were decreased in AFB1-exposed rabbits. In addition, AFB1 induces an inflammatory response in the jejunum and promotes the expression of TNF-α, IL-6 and IL-1β. SeMet pretreatment significantly improved the performance of the rabbits, alleviated intestinal oxidative stress and the inflammatory response. Therefore, we confirmed that SeMet protects against AFB1 induced oxidative damage and improves productivity in rabbits by activating the Nrf2/HO-1 signaling pathway.

Ochratoxin A (OTA) is second only to aflatoxin in toxicity among mycotoxins. Recent studies have shown that selenomethionine (SeMet) has a protective effect on mycotoxin-induced toxicity. The purpose of this study was to investigate the protective effect and mechanism of SeMet on OTA-induced liver injury in rabbits. Sixty 35-day-old rabbits with similar body weight were randomly divided into five groups: control group, OTA group (0.2 mg/kg OTA), OTA + 0.2 mg/kg SeMet group, OTA + 0.4 mg/kg SeMet group and OTA + 0.6 mg/kg SeMet group. Rabbits were fed different doses of the SeMet diet for 21 d, and OTA was administered for one week from day 15 (the control group was provided the same dose of NaHCO₃ solution). The results showed that 0.4 mg/kg SeMet could significantly improve the liver injury induced by OTA poisoning. SeMet supplementation can improve the changes in physiological blood indexes caused by OTA poisoning in rabbits and alleviate pathological damage to the rabbit liver. SeMet also increased the activities of SOD, GSH-Px and T-AOC and significantly decreased the contents of ROS, MDA, IL-1β, IL-6 and TNF-α, effectively alleviating the oxidative stress and inflammatory response caused by OTA poisoning. In addition, OTA poisoning inhibits Nrf2 and HO-1 levels, ultimately leading to peroxide reaction, while SeMet activates the Nrf2 signaling pathway and enhances the expression of the HO-1 downstream Nrf2 gene. These results suggest that Se protects the liver from OTA-induced hepatotoxicity by regulating Nrf2/HO-1 expression.