Genome wide transcriptome analysis provides bases on hepatic lipid metabolism disorder affected by increased dietary grain ratio in fattening lambs.

BACKGROUND: The liver is a principal metabolic organ and has a major role in regulating lipid metabolism. With the development of rapidly fattening livestock in the modern breeding industry, the incidence of hepatic steatosis and accumulation in animals was significantly increased. However, the molecular mechanisms responsible for hepatic lipid metabolic disturbances in a high concentrate diet remain unclear. The objective of this study was to evaluate the effects of increasing concentrate level in a fattening lamb diet on biochemical indices, hepatic triglycerides (TG) concentration, and hepatic transcriptomic profiles. In the present study, 42 weaned lambs (about 3 ± 0.3 months old) were randomly assigned to the GN60 group (60% concentrate of dry matter, GN60, n = 21) or GN70 group (70% concentrate of dry matter, n = 21) for a 3-months feeding trial. RESULTS: No difference was observed in the growth performance or plasma biochemical parameters between the GN60 group and the GN70 group. The hepatic TG concentration was higher in the GN70 group than GN60 group (P < 0.05). Hepatic transcriptomic analysis showed that there were 290 differentially expressed genes identified between GN60 and GN70 groups, with 125 genes up-regulated and 165 genes down-regulated in the GN70 group. The enriched Gene Ontology (GO) items and KEGG pathways and protein-protein interaction (PPI) network of differentially expressed genes (DEGs) revealed that the majority of enriched pathways were related to lipid metabolism. Further analysis revealed that the fatty acid synthesis was up-regulated, while fatty acid transport, oxidation, and TG degradation were down-regulated in the GN70 group when compared with the GN60 group. CONCLUSIONS: These results indicated that GN70 induced excess lipid deposition in the liver of lambs during the fattening period, with high synthesis rates and low degradation rates of TG. The identified mechanisms may help understand hepatic metabolism in lambs with a high concentrate diet and provide insight into decreasing the risk of liver metabolism disorder in animals.

Protective effect of triterpenes of Ganoderma lucidum on lipopolysaccharide-induced inflammatory responses and acute liver injury.

Ganoderma lucidum is a popular medicinal mushroom, which has been used as therapeutic for centuries in traditional Chinese medicine. Although G. lucidum showed strong protective effects in prevention or treatment of a variety of inflammatory diseases, the mechanisms underlying the anti-inflammatory properties of triterpenes of G. lucidum remain undefined. In the current study, we demonstrated that ethanol extract and triterpenes of G. lucidum specifically suppressed LPS-mediated inflammatory responses. Notably, ganodermanontriol inhibited the expressions and interactions of TLR4 and MyD88, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of p38, ErK1/2 and JNK. In vivo, we showed that ganodermanontriol effectively prevented LPS/D-Galactosamine-induced liver injury by reducing TNF-α and IL-6 production, and decrease of ALT/AST release. Collectively, our results revealed a novel role in inhibition of inflammatory diseases for triterpenes that may act through potential inhibition of TLR4-MyD88-mediated NF-κB and MAPK signaling pathways.

Naturally occurring lactic Acid bacteria isolated from tomato pomace silage.

Silage making has become a significant method of forage conservation worldwide. To determine how tomato pomace (TP) may be used effectively as animal feed, it was ensilaged for 90 days and microbiology counts, fermentation characteristics and chemical composition of tomato pomace silage (TPS) were evaluated at the 30th, 60th, and 90th days, respectively. In addition, 103 lactic acid bacteria were isolated from TPS. Based on the phenotypic and chemotaxonomic characteristics, 16S rDNA sequence and carbohydrate fermentation tests, the isolates were identified as 17 species namely: Lactobacillus coryniformis subsp. torquens (0.97%), Lactobacillus pontis (0.97%), Lactobacillus hilgardii (0.97%), Lactobacillus pantheris (0.97%), Lactobacillus amylovorus (1.9%), Lactobacillus panis (1.9%), Lactobacillus vaginalis (1.9%), Lactobacillus rapi (1.9%), Lactobacillus buchneri (2.9%), Lactobacillus parafarraginis (2.9%), Lactobacillus helveticus (3.9%), Lactobacillus camelliae (3.9%), Lactobacillus fermentum (5.8%), Lactobacillus manihotivorans (6.8%), Lactobacillus plantarum (10.7%), Lactobacillus harbinensis (16.5%) and Lactobacillus paracasei subsp. paracasei (35.0%). This study has shown that TP can be well preserved for 90 days by ensilaging and that TPS is not only rich in essential nutrients, but that physiological and biochemical properties of the isolates could provide a platform for future design of lactic acid bacteria (LAB) inoculants aimed at improving the fermentation quality of silage.

Cisplatin resistance-related transcriptome and methylome integration identifies PCDHB4 as a novel prognostic biomarker in small cell lung cancer.

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Antitumor Activity of Disulfiram and Cisplatin in Ovarian Cancer.

INTRODUCTION: Among gynecological cancers, ovarian cancer has a high mortality rate. Cisplatin-based chemotherapy is commonly used for the treatment of ovarian cancer. However, the clinical efficacy of cisplatin in ovarian cancer is limited due to the development of chemo-resistance during treatment. OBJECTIVE: In the study, we aimed to investigate the synergistic anti-cancer activity and targets of the FDA-approved drug disulfiram combined with cisplatin in ovarian cancer. METHODS: The cell viability was determined by Celltier-Glo luminescent assay. The synergistic anti-cancer activity was assessed by combination index. Cell cycle and apoptosis were detected by flow cytometry. The in vivo anti-tumor activity and side effects were evaluated using a xenografted mice model. The synergistic anti-cancer targets were identified by a mass spectrometry-based proteomics analysis. RESULTS: In this study, we first found that disulfiram synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant ovarian cancer cells, which was accompanied by the enhanced induction of cellular apoptosis. Secondly, the in vivo study demonstrated that the combination treatment of disulfiram and cisplatin dramatically inhibited tumor growth and had no apparent side effects in ovarian cancer xenografted mice. Finally, proteomics analysis identified SMAD3 as a potential target of disulfiram-cisplatin combined treatment, and the down-regulation of SMAD3 could increase cisplatin-induced cell death in ovarian cancer. CONCLUSION: Combination treatment of disulfiram and cisplatin synergistically inhibited the growth of ovarian cancer through down-regulating SMAD3. As a repurposed drug, disulfiram could be quickly transformed into a clinic to overcome cisplatin resistance for the treatment of ovarian cancer.

Novel exopolysaccharide derived from probiotic Lactobacillus pantheris TCP102 strain with immune-enhancing and anticancer activities.

Probiotics are gaining attention due to their functions of regulating the intestinal barrier and promoting human health. The production of exopolysaccharide (EPS) is one of the important factors for probiotics to exert beneficial properties. This study aimed to screen exopolysaccharides-producing lactic acid bacteria (LAB) and evaluate the probiotic potential. we obtained three exopolysaccharide fractions (EPS1, EPS2, and EPS3) from Lactobacillus pantheris TCP102 and purified by a combination of ion-exchange chromatography and gel permeation chromatography. The structures of the fractions were characterized by FT-IR, UV, HPLC, and scanning electron microscopy (SEM) analysis. The Mw of EPS1, EPS2, and EPS3 were approximately 20.3, 23.0, and 19.3 kDa, and were mainly composed of galactose, glucose, and mannose, with approximate molar ratios of 2.86:1:1.48, 1.26:1:1, 1.58:1.80:1, respectively. Furthermore, SEM analysis demonstrated that the three polysaccharide fractions differ in microstructure and surface morphology. Additionally, preliminary results for immune-enhancing and anticancer activities reveal that these EPSs significantly induced the production of nitric oxide (NO), TNF-α, and IL-6 in Ana-1 cells and peritoneal macrophage cells. Meanwhile, the EPSs also significantly suppressed the proliferation of HCT-116, BCG-803, and particularly A-2780 cells. The results suggest that the three novel EPSs isolated from Lactobacillus pantheris TCP102 can be regarded as potential application value in functional food and natural antitumor drugs.

Exopolysaccharides from Lactobacillus kiferi as adjuvant enhanced the immuno-protective against Staphylococcus aureus infection.

Exopolysaccharides from lactic acid bacteria (LAB) have gained more attention due to their health benefits. Most research on LAB EPS focuses on antitumor and antioxidant activities. To our knowledge, the immunoadjuvant activity of LAB EPS has not been thoroughly studied. In this study, the EPS produced by Lactobacillus kiferi WXD029 were purified by ethanol precipitation and column chromatography fractionation. The molecular weight of the EPS was 3.423 × 105 Da and was mainly composed of Glu, GlcN, and GalN in a molar ratio of 3.1:1:1. In vitro, EPS could significantly enhance the proliferation and phagocytic activity as well as induce the production of NO, TNF-α, IL-1ß, and IL-6 in RAW264.7 cells. In vivo, the EPS adjuvant could increase the titers of S.aureus antigen-specific antibodies and markedly enhanced T cell proliferation. Notably, EPS adjuvant also induced a strong potential Th1, Th2 and Th17-cell mixture responses. Furthermore, immunization with S.aureus antigen plus EPS adjuvant induced a protective effect when compared with S.aureus antigen alone in murine bacteremia, pneumonia and mastitis model. Collectively, these results suggest that EPS derived from probiotic Lactobacillus kiferi strain is promising as an efficient adjuvant candidate for the prevention of S. aureus infections.

Exopolysaccharides from Lactobacillus buchneri TCP016 Attenuate LPS- and d-GalN-Induced Liver Injury by Modulating the Gut Microbiota.

Liver diseases alter the gut microbiota, but several lactic acid bacteria can reduce the degree of liver damage. The present study investigated whether Lactobacillus buchneri TCP016 reduces the degree of liver damage by modifying the gut microbiota via its exopolysaccharides (EPSs). First, it was illustrated that the main EPS (EPS016; molecular weight = 8.509 × 104 Da) comprised rhamnose, xylose, glucosamine, glucuronic acid, galactose, galacturonic acid, glucose, and mannose in molar ratios of 9.2:3.9:3.8:2.8:2.1:2.0:1.6:1.0. Our data showed that EPS016 alleviated the increase in plasma and hepatic enzyme and cytokine levels, increased superoxide dismutase and glutathione activity, and alleviated bacterial translocation to the liver and mesenteric lymph nodes in vivo. Furthermore, EPS016 ameliorated intestinal mucosal injury and gut flora dysbiosis, thereby decreasing the enrichment of Helicobacteraceae, Lachnospiraceae, and Enterobacteriaceae and increasing the abundance of Lactobacillus, Rikenellaceae, Bacteroidaceae, Bacteroidales_S24-7_group, and Prevotellaceae. These findings indicated that EPS016 inhibits lipopolysaccharides/d-galactosamine-induced liver injury and improves the modification of the gut microbiota.