Peptides from Antarctic krill (Euphausia superba) ameliorate acute liver injury in mice induced by carbon tetrachloride via activating the Nrf2/HO-1 pathway.

This study aimed to evaluate the hepatoprotective effects of peptides from Antarctic krill (AKP) on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice and the underlying molecular mechanisms. ICR mice were pretreated with AKP (500 mg kg-1, i.g.) and silybin (30 mg kg-1, i.g.) for 15 days before CCl4 (0.25 mL per kg BW, i.p.) injection. To assess hepatocellular damage and molecular indices, the serum and liver tissue were evaluated at harvest. The results showed that AKP pretreatment remarkably attenuated CCl4-induced liver injury, which was identified by the decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviation of hepatocyte necrosis, and inhibition of the levels of the pro-inflammatory factors TNF-α and IL-1ß compared to those for silymarin. AKP pretreatment also enhanced the redox balance by reducing the concentrations of MDA and 8-iso-PG and increasing the activities of SOD, GSH and GSH-PX in the liver of mice. In addition, AKP upregulated oxidative stress-related mRNA expressions of Nrf2, Keap1, HO-1, and NQO1 and further activated the protein expression on the Nrf2/HO-1 singling pathway. In summary, AKP might be a promising hepatoprotective nutraceutical against ALI and its underlying mechanisms are associated with activation of the Nrf2/HO-1 pathway.

Antarctic krill peptide alleviates liver fibrosis via downregulating the secondary bile acid mediated NLRP3 signaling pathway.

Liver fibrosis is a necessary process for liver disease. Recent studies have reported that the enterohepatic circulation of bile acid plays a vital role in developing liver fibrosis. The Antarctic krill peptide (AKP) has been proved to have a variety of activities such as antioxidant and anti-inflammatory, but any possible influence on liver fibrosis remains unclear. In the current study, the liver fibrosis mice were intraperitoneal injection of carbon tetrachloride (2.5%, 10 mL kg-1) and oral administration AKP (400 mg kg-1) for 30 days. The results showed that the AKP supplement decreased the serum ALT and AST levels, reduced the content of liver TNF-α and Collagen I, and improved liver inflammation and fibrosis, which was also confirmed by H&E and Masson staining. Bile acid is an important metabolite for the gut microbiota. We found that the AKP supplement alleviated the gut microbiota dysbiosis remarkably, as indicated by increased species richness and diversity, and decreased overgrowth of genera Bifidobacterium, Lactobacillus, Bacteroides, Clostridiales and Fusicatenibacter. Furthermore, AKP mediated gut microbiota improvement decreased the intestinal bile salt hydrolase and 7α-dehydroxylation activities, resulting in the decrease of secondary bile acid taurodeoxycholic acid (TDCA) and taurolithocholic acid (TLCA) concentrations. Mechanistically, AKP inhibited NLRP3 signal by downregulating the secondary bile acid, decreased cleaved Caspase-1 expression to suppress IL-1ß-mediated hepatic stellate cell activation. This study reports for the first time that AKP improved liver fibrosis via improving the gut microbiota mediated bile acid-NLRP3 signaling, which might provide new ideas and evidence for Antarctic krill's high-value utilization.

Fur Protein Regulates the Motility of Avian Pathogenic Escherichia coli AE17 Through Promoter Regions of the Flagella Key Genes flhD.

Avian pathogenic Escherichia coli (APEC) is an important pathogen causing several diseases in birds. It is responsible for local and systemic infections in poultry, seriously impeding the development of the poultry industry, and poses a potential risk to public health. The iron absorption regulatory protein Fur and the noncoding RNA, RyhB, that it negatively regulates are important factors in bacterial iron uptake, but the regulation of bacterial virulence genes varies greatly among different bacteria. We found that Fur is very important for the mobility of APEC. The expression of fur and RyhB is extensively regulated in APEC, and RyhB expression is also negatively regulated by Fur. A transcriptomic analysis showed that the genes significantly differentially regulated by Fur are related to cell movement, including pilus- or flagellum-dependent cell motility. To verify these results, we examined the effects of fur knockdown on cell movement by measuring the diameter of the bacteria colonies. Consistent with the RNA sequencing results, the mobility of AE17Δfur was significantly reduced compared with that of the wild type, and it had almost lost its ability to move. Using an electrophoretic mobility assay, we confirmed that the Fur protein directly binds to the promoter region of the key flagellum-related gene flhD, thereby affecting the assembly and synthesis of the APEC flagellum. This study extends our understanding of gene regulation in APEC.

Sialoglycoproteins isolated from the eggs of Carassius auratus alleviates CCL4-induced liver injury via downregulation of the IRE-α/NF-κB signaling pathway.

Chemical liver injury is a common cause of liver disease primarily characterized by oxidative stress and inflammation. Sialoglycoproteins isolated from the eggs of Carassius auratus (Ca-SGP) have been proved to exhibit the antioxidant effect. However, the effect of Ca-SGP on liver injury remains unclear. Thus, this study was aimed to determine the effect of Ca-SGP on CCL4-induced chronic chemical liver injury and explore the underlying molecular mechanism. Results showed that Ca-SGP mitigated the elevated levels of serum alanine aminotransferase and aspartate aminotransferase, inhibited the systemic oxidative stress, and reduced the levels of pro-inflammatory factors TNF-α and IL-1ß. Histologic results showed that Ca-SGP supplements alleviated hepatocyte necrosis and liver macrophage infiltration. Further, Ca-SGP supplement decreased endoplasmic reticulum stress-related proteins expression, including BiP, IRE-α, p-IRE-α, and TRAF2, and further inhibited the trigger of the NF-κB pathway. In summary, Ca-SGP might be a novel agent for liver injury treatment, and its potential mechanism was related to the inhibition of liver inflammation induced by the endoplasmic reticulum. PRACTICAL APPLICATION: The fish egg is an important by-product in fish processing. Carassius auratus is a common freshwater fish with large catches and low prices. However, the eggs of C. auratus are usually direct discard or processed into salted roe products, and the quality and value of these salted products are unsatisfactory. In this current study, we confirmed that sialoglycoproteins isolated from the C. auratus eggs have the potential for the treatment of liver injury and determined that its mechanism is related to the endoplasmic reticulum and inflammation, which put forward a new idea for solving the by-product of fish processing.

A Novel Sialoglycopeptide from Gadus morhua Eggs Prevents Liver Fibrosis Induced by CCl4 via Downregulating FXR/FGF15 and TLR4/TGF-ß/Smad Pathways.

Liver fibrosis plays a critical role in liver disease progression. A sialoglycopeptide from the Gadus morhua eggs (Gm-SGPP) was identified having a 7000 Da molecular weight with a core pentasaccharide structure and osteogenesis activity. However, whether Gm-SGPP is beneficial to liver fibrosis remains unknown. In this study, mice with liver fibrosis were intraperitoneally injected with 2.5% CCl4 (10 mL/kg) and orally administered with Gm-SGPP (500 mg/kg) for 30 days. Results showed that Gm-SGPP alleviated oxidative liver damage and lipid metabolism disorder and reduced hepatocyte necrosis and lipid droplet accumulation. Notably, we found that Gm-SGPP increased the number and changed the composition of bile acids via increasing cholesterol 7a-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) expression, which caused inhibition of ileum farnesoid X receptor (FXR) expression and accelerated the cholesterol conversion. Cholesterol accumulation is a risk factor for liver fibrosis. Masson staining showed that Gm-SGPP significantly reduced the degree of collagen deposition. Western blotting further suggested that Gm-SGPP downregulated the key gene of the toll-like receptor 4 (TLR4)-mediated transforming growth factor-ß (TGF-ß)/Smad pathway. To our best knowledge, this is the first report that Gm-SGPP prevented liver fibrosis via attenuating cholesterol accumulation. Our present results provide new ideas for the Gadus morhua egg's high-value utilization.

Novel ι-Carrageenan Tetrasaccharide Alleviates Liver Lipid Accumulation via the Bile Acid-FXR-SHP/PXR Pathway to Regulate Cholesterol Conversion and Fatty Acid Metabolism in Insulin-Resistant Mice.

ι-Carrageenan tetrasaccharide (ιCTs), a novel oligosaccharide, was hydrolyzed from ι-carrageenan with targeting marine tool-enzyme Cgi82A. Previously, we have found ιCTs exhibited a hypoglycemic effect, whether it could regulate lipid metabolism remains unknown. In this study, the insulin-resistant mice induced by high-fat-high-sucrose diet were orally administrated with ιCTs (30 mg/kg·bw) for 20 weeks. The results showed that the contents of triglyceride and cholesterol in both serum and liver were reduced by ιCTs, and their excretion in feces were promoted, suggesting lipid accumulation was inhibited. Intriguingly, the overall levels of bile acid in serum, liver, and feces were all raised by ιCTs. Given that bile acids are the essential signal factors for regulating lipid metabolism via the farnesoid-X-receptor (FXR), we conducted serum bile acid profile analysis and found that the levels of high-affinity agonists deoxycholic acid and lithocholic acid were decreased in the ιCTs group, showing that ιCTs failed to activate FXR. Western blot analysis showed that ιCTs downregulated hepatic FXR and small heterodimer partner (SHP) expression and increased downstream CYP7A1 expression via regulating the FXR-SHP signal to accelerate liver cholesterol conversion. Meanwhile, ιCTs decreased the expression of PXR and SREBP1c and elevated the expression of PPARα and CPT1α via regulating the FXR-PXR-SREBP1c/PPARα signal to inhibit fatty acid synthesis and promote fatty acid ß-oxidation. To the best of our knowledge, this study for the first time reported that ιCTs alleviated liver lipid accumulation via the bile acid-FXR-SHP/PXR signal to regulate cholesterol conversion and fatty acid metabolism, which highlighted a new idea for ameliorating insulin resistance.

Orbital coupling of hetero-diatomic nickel-iron site for bifunctional electrocatalysis of CO2 reduction and oxygen evolution.

While inheriting the exceptional merits of single atom catalysts, diatomic site catalysts (DASCs) utilize two adjacent atomic metal species for their complementary functionalities and synergistic actions. Herein, a DASC consisting of nickel-iron hetero-diatomic pairs anchored on nitrogen-doped graphene is synthesized. It exhibits extraordinary electrocatalytic activities and stability for both CO2 reduction reaction (CO2RR) and oxygen evolution reaction (OER). Furthermore, the rechargeable Zn-CO2 battery equipped with such bifunctional catalyst shows high Faradaic efficiency and outstanding rechargeability. The in-depth experimental and theoretical analyses reveal the orbital coupling between the catalytic iron center and the adjacent nickel atom, which leads to alteration in orbital energy level, unique electronic states, higher oxidation state of iron, and weakened binding strength to the reaction intermediates, thus boosted CO2RR and OER performance. This work provides critical insights to rational design, working mechanism, and application of hetero-DASCs.

DHA/EPA-Enriched Phosphatidylcholine Suppresses Tumor Growth and Metastasis via Activating Peroxisome Proliferator-Activated Receptor γ in Lewis Lung Cancer Mice.

In the present study, the antitumor effects of docosahexaenoic acid-phosphatidylcholine (DHA-PC) and eicosapentanoic acid-phosphatidylcholine (EPA-PC) in Lewis lung cancer mice were investigated. As observed, DHA-PC and EPA-PC obviously inhibited the transplanted tumor growth and the positive expression of Ki67. The metastatic nodules and hematoxylin and eosin (HE) staining of the lung indicated that DHA-PC and EPA-PC suppressed lung metastasis. PPARγ has a key role in cell survival, which may be a target for cancer therapy. Further mechanism research indicated that DHA-PC and EPA-PC significantly enhanced the levels of PPARγ and subsequently downregulated the NF-κB pathway. DHA-PC and EPA-PC accelerate cancer cell apoptosis by decreasing NF-κB-mediated antiapoptotic factors Bcl-2 and Bcl-XL, thereby inhibiting tumor growth. In addition, DHA-PC and EPA-PC significantly decreased the levels of NF-κB-mediated matrix metallopeptidase 9 (MMP9) and heparanase (HPA), which block the extracellular matrix (ECM) degradation, thereby suppressing lung metastasis. These findings suggested that DHA-PC and EPA-PC could be used as food supplements and/or functional ingredients for cancer patients.

Differences in the dielectric properties of various benign and malignant thyroid nodules.

PURPOSE: This experiment was conducted to investigate the dielectric properties of different types of thyroid nodules. Our goal was to find a simple and fast method to detect thyroid diseases at different stages from the dielectric properties of thyroid nodules. METHODS: We used the open-ended coaxial line method to measure the dielectric permittivities of thyroid tissues from 155 patients at frequencies ranging from 1 to 4000 MHz. Tissues that were investigated included normal thyroid tissue and benign and malignant thyroid nodules (nodular goiter, follicular adenoma, papillary carcinoma, and follicular carcinoma), as determined from pathological reports. Differences in dielectric properties were measured between each nodule and the surrounding 1 cm of tissue. RESULTS: The analysis results revealed that the dielectric permittivity and conductivity values were positively correlated with the degree of malignancy of the nodule (normal < benign < malignant; all differences P < 0.05). This was more obvious at frequencies within 20~70 MHz, following the order normal tissue < nodular goiter < follicular adenoma < papillary carcinoma < follicular carcinoma. A significant difference (P < 0.05) in dielectric permittivity and conductivity was found when comparing these nodules with the surrounding 1 cm of tissue. CONCLUSIONS: Normal, benign, and malignant nodules were successfully distinguished from one another, and dielectric permittivity was found to be a more sensitive parameter than conductivity. In particular, different disease types can be distinguished at a stimulation frequency of 20~70 MHz, which shows that dielectric properties have application prospects for the detection and diagnosis of cancer. At the same time, the dielectric parameter differences between the surrounding 1 cm of tissue and the diseased nodule can distinguish the tumor and its surrounding tissues in real time during surgery to determine the tumor boundary.