Xiaoguang Chen

Zearalenone (ZEA), a mycotoxin primarily generated by the Fusarium species, constitutes a prevalent contaminant in both human and animal feedstuffs. Chronic exposure to this mycotoxin induces hepatic inflammatory responses in livestock species including rabbits, ultimately leading to organ damage. Selenomethionine (SeMet), an organic selenium source recognized for its antioxidant properties and anti-inflammatory bioactivity, demonstrates protective benefits in animals through its detoxification mechanism and growth promotion. The present study investigated the protective effect of SeMet against ZEA-induced hepatic inflammation and elucidated its underlying mechanisms. Fifty healthy 90-day-old rabbits were randomly divided into five groups: control, ZEA-exposed and three SeMet-supplemented groups receiving 0.2, 0.35 or 0.5 mg/kg via dietary inclusion. After two weeks of SeMet pretreatment, ZEA administration (1.2 mg/kg B.W.) was imitated via oral gavage daily for one week in both the ZEA group and three SeMet-treated groups. As a result, ZEA exposure induced the significant structural disruption of the hepatic lobules, accompanied by increased collagen deposition, elevated pro-inflammatory cytokine profiles (IL-6, IL-1β, TNF-α) and reduced anti-inflammatory mediator levels (IL-10, TGF-β). SeMet supplementation alleviated ZEA-induced histological alterations, including inflammatory cell infiltration and collagen accumulation. Biochemical analysis indicated the restoration of inflammatory markers to near-normal levels when treated with SeMet. Notably, immunohistochemical results showed that SeMet significantly reduced the protein levels of IL-6 and its downstream target STAT3 under ZEA exposure. These findings indicated that SeMet attenuated ZEA-induced hepatic inflammation by modulating the IL-6/STAT3 signaling axis, with dietary supplementation of 0.35 mg/kg SeMet exhibiting the most significant effect on alleviating ZEA-induced hepatic inflammatory injury.

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.

Zearalenone (ZEA) is a mycotoxin produced by Fusarium spp. fungi and is widely found in moldy corn, wheat, barley, and other grains. ZEA is distributed to the whole body via blood circulation after metabolic transformation in animals. Through oxidative stress, immunosuppression, apoptosis, autophagy, and mitochondrial dysfunction, ZEA leads to hepatitis, neurodegenerative diseases, cancer, abortion, and stillbirth in female animals, and decreased sperm motility in male animals. In recent years, due to the influence of climate, storage facilities, and other factors, the problem of ZEA pollution in global food crops has become particularly prominent, resulting in serious problems for the animal husbandry and feed industries, and threatening human health. Resveratrol (RSV) is a natural product with therapeutic activities such as anti-inflammatory, antioxidant, and anticancer properties. RSV can alleviate ZEA-induced toxic effects by targeting signaling pathways such as NF-κB, Nrf2/Keap1, and PI3K/AKT/mTOR via attenuating oxidative damage, inflammatory response, and apoptosis, and regulating cellular autophagy. Therefore, this paper provides a review of the protective effect of RSV against ZEA-induced toxicity and its molecular mechanism, and discusses the safety and potential clinical applications of RSV in the search for natural mycotoxin detoxification agents.

As the most important organ of detoxification in the body, the liver also has the strong regenerative ability itself. The liver can regenerate after partia

It has been reported that dodecanoic acid (DDA) exerts anticancer effects on cancers of the reproductive system and digestive system. However, its role in liver cancer and its potential mechanism have rarely been defined. Therefore, in this study, Hepa 1-6 liver cancer cells were incubated with different DDA concentrations (0.1, 0.3, 0.5, 1, 2, 4 mM) for 24, 48 and 72h, and the optimal DDA concentration was determined via a cell viability test. Apoptosis and cell cycle distribution were determined by flow cytometry. SOD activity, mitochondrial membrane potential (MMP), ATP, GSH and ROS levels were measured by commercial assay kits; Bcl-2, Bax and Caspase-3 protein levels were analyzed by western blot. The results showed that 0.5 mM DDA decreased cell viability in a time-dependent manner, so this concentration was used to investigate how DDA leads to Hepa 1-6 cell apoptosis. After treatment with DDA, a significant, time-dependent increase in the cell apoptotic rate was detected despite the accumulation of S-phase cells. The increased ROS levels and decreased GSH levels and SOD activity in DDA-treated cells indicated the occurrence of oxidative stress. Mitochondrial dysfunction was evidenced by a decreased MMP and reduced ATP levels. Cell apoptotic death via the mitochondrial pathway was indicated by a reduced Bcl-2/Bax ratio and increased caspase-3 protein levels. It can be concluded that DDA can effectively trigger liver cancer cell death by inducing oxidative stress and disrupting mitochondrial function. These findings provide new insight into the potential mechanism of action of DDA in liver cancer.

Phospholipase Cγ2 has the promotive effect on hepatic carcinoma development. Meanwhile, lncRNAs play a critical role in the pathology. Therefore, to m

Objective: Even a small fragment from the body of planarian can regenerate an entire animal, implying that the different fragments from this flatworm eventually reach the same solution. In this study, our aim was to reveal the differences and similarities in mechanisms between different regenerating fragments from this worm. Materials and Methods: In this experimental study, we profiled the dynamic proteome of regenerating head and tail to reveal the differences and similarities between different regenerating fragments using 2-DE combined with MALDI-TOF/TOF MS. Results: Proteomic profiles of head and tail regeneration identified a total of 516 differential expressed proteins (DEPs) and showed a great difference in quantity and fold changes of proteome profiles between the two scenarios. Briefly, out of the 516 DEPs, 314 were identified to be specific for anterior regeneration, while 165 were specific for posterior regeneration. Bioinformatics analysis showed a wide discrepancy in biological activities between two regenerative processes; especially, differentiation & development and signal transduction in head regeneration were much more complex than that in tail regeneration. Protein functional analysis combined with protein-protein interaction (PPI) analysis showed a significant contribution of both Wnt and BMP signaling pathways to head regeneration not but tail regeneration. Additionally, several novel proteins showed completely opposite expression between head and tail regeneration. Conclusion: Proteomic profiles of head and tail regeneration identified a total of 516 differential expressed proteins (DEPs) and showed a great difference in quantity and fold changes of proteome profiles between the two scenarios. Briefly, out of the 516 DEPs, 314 were identified to be specific for anterior regeneration, while 165 were specific for posterior regeneration. Bioinformatics analysis showed a wide discrepancy in biological activities between two regenerative processes; especially, differentiation & development and signal transduction in head regeneration were much more complex than that in tail regeneration. Protein functional analysis combined with protein-protein interaction (PPI) analysis showed a significant contribution of both Wnt and BMP signaling pathways to head regeneration not but tail regeneration. Additionally, several novel proteins showed completely opposite expression between head and tail regeneration.

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.