Small-Molecule Modulation of Protein Lipidation: From Chemical Probes to Therapeutics.

Protein lipidation is a widespread modification that regulates protein subcellular localization, structure and function. Dysregulation of protein lipidation has been implicated in various human diseases, including neurological disorders, infectious diseases and cancers. Thus lipid-modifying enzymes and their substrate proteins are emerging as attractive drug targets. The development of small-molecule modulators of protein lipidation has remarkably impacted our understanding of lipid-modification biology and potential therapeutics. In this review, we summarize recent progress in small-molecule targeting of protein lipidation and highlight therapeutic opportunities.

Bacillus amyloliquefaciens SC06 Induced AKT-FOXO Signaling Pathway-Mediated Autophagy to Alleviate Oxidative Stress in IPEC-J2 Cells.

Autophagy is a conserved proteolytic mechanism, which degrades and recycles damaged organs and proteins in cells to resist external stress. Probiotics could induce autophagy; however, its underlying molecular mechanisms remain elusive. Our previous study has found that BaSC06 could alleviate oxidative stress by inducing autophagy in rats. This research aimed to verify whether Bacillus amyloliquefaciens SC06 can induce autophagy to alleviate oxidative stress in IPEC-J2 cells, as well as explore its mechanisms. IPEC-J2 cells were first pretreated with 108 CFU/mL BaSC06, and then were induced to oxidative stress by the optimal dose of diquat. The results showed that BaSC06 significantly triggered autophagy, indicated by the up-regulation of LC3 and Beclin1 along with downregulation of p62 in IPEC-J2 cells. Further analysis revealed that BaSC06 inhibited the AKT-FOXO signaling pathway by inhibiting the expression of p-AKT and p-FOXO and inducing the expression of SIRT1, resulting in increasing the transcriptional activity of FOXO3 and gene expression of the ATG5-ATG12 complex to induce autophagy, which alleviated oxidative stress and apoptosis. Taken together, BaSC06 can induce AKT-FOXO-mediated autophagy to alleviate oxidative stress-induced apoptosis and cell damage, thus providing novel theoretical support for probiotics in the prevention and treatment of oxidative damage.

The role of iron homeostasis and iron-mediated ROS in cancer.

As an important trace element, iron plays an essential role in many biology processes like cell proliferation, metabolism, and mitochondrial function. However, the disruption of iron homeostasis tends to cells death and human diseases due to it servers as mediator to promote the production of reactive oxygen species (ROS). In this review, first we introduced the mechanism of complex iron-mediated ROS involved in apoptosis, necroptosis, ferroptosis and pyroptosis. Next, we discussed the controversial role of excess iron and iron deficiency in tumor. Finally, we discussed the anti-cancer effects of iron on both sides, and novel iron-related strategies. This review outlined the mechanisms and regulation of iron homeostasis and iron-mediated ROS in tumors, and discussed the iron-related treatments.

Effects of Dietary Supplementation of Humic Acid Sodium and Zinc Oxide on Growth Performance, Immune Status and Antioxidant Capacity of Weaned Piglets.

At present, the widespread use of high-dose zinc oxide and antibiotics to prevent post-weaning diarrhea (PWD) in piglets has caused serious environmental problems. To solve this problem, we studied the effect of HNa as a substitute for zinc oxide (ZnO) and antibiotics on the growth performance, immune status, and antioxidant capacity of piglets. Seventy-two weaned piglets (body weight = 7.42 ± 0.85 kg, 26-d-old) were distributed in a randomized 2 × 3 factorial design (two sexes and three treatments) with six replicates of four piglets each. The three treatments were the control diet (basic diet), HNa diet (basic diet + 2000 mg/kg sodium humate), and ZoA group (basic diet + 1600 mg/kg zinc oxide + 1000 mg/kg oxytetracycline calcium). ANOVA and Chi-square tests were applied to compare the means (p < 0.05) between treatments. The results showed that body weight at 16 and 30 d and the average daily gain of piglets fed with HNa or ZoA were significantly higher (p < 0.05) than the control group. Supplementing HNa or ZoA significantly increased (p < 0.05) the level of immunoglobulin M and G, and reduced (p < 0.05) the concentration of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukins IL-6 and IL-1ß, myeloperoxidase (MPO), and diamine oxidase (DAO). Furthermore, dietary HNa or ZnO significantly reduced (p < 0.05) the level of total antioxidant capacity (T-AOC) and malondialdehyde (MDA) compared with the control group. ZoA treatment showed an upward trend of IgA level and a downward trend of the concentration of lipopolysaccharide (LPS) and catalase (CAT). Overall, the study demonstrated that the addition of HNa in the diet partially replaced antibiotics and ZnO to improve the growth performance, immune function, and antioxidant capacity of weaned piglets, and maintained a good preventive effect on piglet diarrhea.

High expression of FOXO3 is associated with poor prognosis in patients with hepatocellular carcinoma.

The role of forkhead box O3 (FOXO3) as a tumor suppressor gene and its association with the human lifespan is well documented. However, several studies have indicated that high expression of FOXO3 is also significantly associated with tumorigenesis. The aim of the present study was to determine the clinical significance of FOXO3 in the development and prognosis of hepatocellular carcinoma (HCC). mRNA expression data of FOXO3 from The Cancer Genome Atlas database was analyzed through the UALCAN online tool to compare the expression of FOXO3 between HCC and normal liver tissues. Subsequently, the expression of FOXO3 at the protein level was investigated via immunohistochemical staining of 314 HCC and 150 non-cancerous liver tissue samples. The association between protein expression and clinicopathological parameters was analyzed using the χ2 test, and the effect of FOXO3 expression on survival was assessed via Kaplan-Meier analysis. The expression of FOXO3 mRNA was significantly higher in HCC in comparison with healthy tissues. High FOXO3 protein expression was revealed in 43/150 non-cancerous liver tissues, and in 238/314 HCC samples. A significant association was demonstrated between FOXO3 expression and metastasis, Tumor-Node-Metastasis stage, Edmondson grade, α-fetoprotein level and overall survival. In conclusion, the high expression of FOXO3 predicts a poor prognosis in patients with HCC, indicating this protein as a potential therapeutic target in HCC.

Application of Bacillus coagulans in Animal Husbandry and Its Underlying Mechanisms.

In recent decades, probiotics have attracted widespread attention and their application in healthcare and animal husbandry has been promising. Among many probiotics, Bacillus coagulans (B. coagulans) has become a key player in the field of probiotics in recent years. It has been demonstrated to be involved in regulating the balance of the intestinal microbiota, promoting metabolism and utilization of nutrients, improving immunity, and more importantly, it also has good industrial properties such as high temperature resistance, acid resistance, bile resistance, and the like. This review highlights the effects of B. coagulans in animal husbandry and its underlying mechanisms.