Dietary Supplementation of Bacillus sp. PM8313 with ß-glucan Modulates the Intestinal Microbiota of Red Sea Bream (Pagrus major) to Increase Growth, Immunity, and Disease Resistance.

A 56-day feeding trial was conducted to determine the effect of dietary supplementation with Bacillus sp. isolated from the intestines of red sea bream on the growth performance, immunity, and gut microbiome composition of red sea bream. Three diets (a control diet and two treatments) were formulated without Bacillus sp. PM8313 or ß-glucan (control, CD), 1 × 108 CFU g-1 PM8313 (BSD), and 1 × 108 CFU g-1 PM8313 + 0.1% ß-glucan (BGSD). At the end of the experiment, the weight, specific growth rate, feed conversion ratio, and protein efficiency ratio of the fish in the BSD and BGSD diet groups were significantly improved than those of the control group (P < 0.05). Additionally, amylase and trypsin activities were significantly higher (P < 0.05) in both groups compared to the control. Superoxide dismutase and lysozyme activity, which are serum non-specific immune responses, only increased in the BGSD group. The two treatment groups exhibited a marked difference in the intestinal microbiota composition compared to the control group. Furthermore, the treatment groups exhibited an upregulation of IL-6 and NF-κb, coupled with high survival rates when challenged with Edwardsiella tarda. Therefore, dietary supplementation with PM8313 improved the growth performance, digestive enzyme activity, non-specific immunity, and pathogen resistance of red sea bream, in addition to affecting the composition of its intestinal microflora.

Characterization of a Bacillus sp. KRF-7 isolated from the intestine of rockfish and effects of dietary supplementation with mannan oligosaccharide in rockfish aquaculture.

The purpose of this study was to characterize the bacteria isolated from rockfish intestines and to investigate the effects of feed supplementation in rockfish aquaculture. Bacillus sp. KRF-7 isolated from the intestine of rockfish (Sebastes schlegelii) was demonstrated to be safe based on in vitro tests confirming the absence of hemolysis, cytotoxicity, and genes with toxigenic potential. In a feeding trial, providing a supplemental diet of 1 × 108 CFU g-1Bacillus sp. KRF-7 was observed to positively alter the weight gain, specific growth rate, feed conversion ratio, and protein efficiency ratio of juvenile rockfish. KRF-7 supplementation showed positive regulation of nonspecific immune parameters, such as superoxide dismutase, lysozyme activity, and myeloperoxidase activity. This analysis also revealed a change in the composition of the intestinal microbiota at the phylum level from Proteobacteria to Firmicutes. In both the kidney and spleen, the expression levels of IL-10, NF-κB, and B cell activating factors in the KRF-7-supplemented group were significantly increased compared to those in the control group. Therefore, this study verified the safety of KRF-7 isolated from the intestine of rockfish and suggests that dietary supplementation with KRF-7 enhances the growth performance of rockfish and has beneficial effects on the regulation of the intestinal microbiota and immune response.

Dietary Supplementation of Bacillus sp. SJ-10 and Lactobacillus plantarum KCCM 11322 Combinations Enhance Growth and Cellular and Humoral Immunity in Olive Flounder (Paralichthys olivaceus).

Experiments were conducted to identify different ratios of Bacillus sp. SJ-10 and Lactobacillus plantarum KCCM 11322 mixtures at a concentration of 1 × 108 CFU/g diet; the effects on growth and cellular and humoral immune responses and the characteristics of disease protection in olive flounder (Paralichthys olivaceus). Flounder were divided into six groups and fed control diet D-1 (without Bacillus sp. SJ-10 and L. plantarum KCCM 11322), positive control diets D-2 (Bacillus sp. SJ-10 at 1 × 108 CFU/g feed) and D-3 (L. plantarum KCCM 11322 at 1 × 108 CFU/g feed); or treatment diets D-4 (3:1 Bacillus sp. SJ-10 and L. plantarum KCCM 11322 at 0.75 + 0.25 × 108 CFU/g feed), D-5 (1:1 Bacillus sp. SJ-10 and L. plantarum KCCM 11322 at 0.50 + 0.50 × 108 CFU/g feed), or D-6 (1:3 Bacillus sp. SJ-10 and L. plantarum KCCM 11322 at 0.25 + 0.75 × 108 CFU/g feed) for 8 weeks. Group D-4 demonstrated better growth and feed utilization (P < 0.05) compared with the controls and positive controls. Similar modulation was also observed in respiratory burst for all treatments and in the expression levels of TNF-α, IL-1ß, IL-6, and IL-10 in different organs in D-4. D-4 and D-5 increased respiratory burst, superoxide dismutase, lysozyme, and myeloperoxidase activities compared with the controls, and only D-4 increased microvilli length. When challenged with 1 × 108 CFU/mL Streptococcus iniae, the fish in the D-4 and D-5 groups survived up to 14 days, whereas the fish in the other groups reached 100% mortality at 11.50 days. Collectively, a ratio-specific Bacillus sp. SJ-10 and L. plantarum KCCM 11322 mixture (3:1) was associated with elevated growth, innate immunity, and streptococcosis resistance (3:1 and 1:1) compared with the control and single probiotic diets.

Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer.

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.

Inhibition of Jurkat T Cell Proliferation by Active Components of Rumex japonicus Roots Via Induced Mitochondrial Damage and Apoptosis Promotion.

Rumex japonicus Houtt (RJH) is a valuable plant used in traditional medicine to treat several diseases, such as scabies and jaundice. In this study, Jurkat cell growth inhibitory extracts of R. japonicus roots were subjected to bioassay-guided fractionation, resulting in the isolation of three naphthalene derivatives (3-5) along with one anthraquinone (6) and two phenolic compounds (1 and 2). Among these compounds, 2-methoxystypandrone (5) exhibited potent anti-proliferative effects on Jurkat cells. Analysis by flow cytometry confirmed that 2-methoxystypandrone (5) could significantly reduce mitochondrial membrane potential and promote increased levels of mitochondrial reactive oxygen species (ROS), suggesting a strong mitochondrial depolarization effect. Real-time quantitative polymerase chain reaction (qPCR) analysis was also performed, and the results revealed that the accumulation of ROS was caused by reduced mRNA expression levels of heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, 2-methoxystypandrone (5) triggered strong apoptosis that was mediated by the arrest of the G0/G1 phase of the cell cycle. Furthermore, 2-methoxystypandrone (5) downregulated p-IκB-α, p-NF-κB p65, Bcl2, and Bcl-xl and upregulated BAX proteins. Taken together, these findings revealed that 2-methoxystypandrone (5) isolated from RJH could potentially serve as an early lead compound for leukemia treatment involving intracellular signaling by increasing mitochondrial ROS and exerting anti-proliferative effects.

Effects of dietary non-viable Bacillus sp. SJ-10, Lactobacillus plantarum, and their combination on growth, humoral and cellular immunity, and streptococcosis resistance in olive flounder (Paralichthys olivaceus).

Heat-killed (HK) Bacillus sp. SJ-10 (B), HK Lactobacillus plantarum (P), and their combination were dietary supplemented to olive flounder (Paralichthys olivaceus) to quantify the effects on growth, innate immunity, and disease resistance. Four test diets were supplied: a control feed free of HK probiotics, 1 × 108 CFUs g-1 single treatments of each of HK B (HKB) and HK P (HKP), and an equal proportion of (0.5 HKB + 0.5 HKP) × 108 CFUs g-1 (HKB0.5 HKP0.5). At 8 weeks of completion feeding trail, HKB0.5 HKP0.5 significantly (P < .05) improved growth, feed utilization, and nonspecific immune parameters (respiratory burst and superoxide dismutase) compared to the control group. Similarly, serum lysozyme and myeloperoxidase activities were higher in both HKB and HKB0.5HKP0.5 groups. The levels of pro-inflammatory cytokine IL-6 in the liver and IL-1ß in the liver, kidney, and spleen were also improved in the treatments, but microvilli length was only increased in HKB0.5HKP0.5. After Streptococcus iniae 1 × 108 CFUs mL-1 challenged; HKB and HKB0.5HKP0.5 had a higher survival than control and HKP. Overall, dietary administration of synergy HK probiotics elevated growth, cellular and humoral immunity, and streptococcosis resistance in olive flounder.

Pancreatic lipase inhibitory stilbenoids from the roots of Vitis vinifera.

Bioassay-guided isolation of an aqueous methanolic extract of Vitis vinifera using pancreatic lipase inhibitory activity led to isolation of seven stilbenoids, wilsonol C (1), heyneanol A (2), ampelopsin A (3), pallidol A (4), cis-piceid (5), trans-piceid (6) and trans-resveratrol (7). The structures were established on the basis of NMR and MS spectroscopic data interpretation. All isolates were evaluated for their inhibitory effects on pancreatic lipase, and stilbenoid 1 exhibited potent inhibitory effect on pancreatic lipase with IC50 values of 6.7 ± 0.7 µM.

Pancreatic lipase inhibitory gallotannins from Galla Rhois with inhibitory effects on adipocyte differentiation in 3T3-L1 cells.

Activity-guided isolation of a methanolic extract of Galla Rhois using pancreatic lipase and 3T3-L1 adipocytes led to the isolation of seven phenolic compounds: protoaphin-fb (1), 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-ß-D-glucose (2), 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (3), 1,2,4,6-tetra-O-galloyl-ß-D-glucose (4), 3-hydroxy-5-methoxy-phenol 1-O-ß-D-glucoside (5), methylgallate (6), and gallic acid (7). Their structures were established on the basis of NMR and MS spectroscopic data interpretation. All isolates were evaluated for their inhibitory effects on pancreatic lipase, and compounds 1-5 exhibited potent inhibitory effects on this enzyme, with IC50 values ranging from 30.6 ± 2.4 to 3.5 ± 0.5 mM. In addition, the highly galloylated compound 2 was also found to induce potent inhibition of adipocyte differentiation in 3T3-L1 cells.

Anti-methicillin-resistant Staphylococcus aureus (MRSA) substance from the marine bacterium Pseudomonas sp. UJ-6.

A multivalent approach to discover a novel antibiotic substance against methicillin-resistant Staphylococcus aureus (MRSA), a marine bacterium, UJ-6, exhibiting an antibacterial activity against MRSA was isolated from seawater. The isolated strain was identified to be Pseudomonas sp. by the morphology, biochemical, and genetical analyses. The ethyl acetate extract of Pseudomonas sp. UJ-6 culture showed significant ant-MRSA activity. Bioassay-guided isolation of the extract using a growth inhibitory assay led to the isolation and identification of an active compound exhibiting anti-MRSA activity. Based on the analyses of the physicochemical and spectroscopic data including nuclear magnetic resonance and mass, the compound was identified to be 1-acetyl-beta-carboline. The minimum inhibitory concentration (MIC) of the compound was determined to be in a range of 32-128 µg/ml against MRSA strains. The MIC values against MRSA were superior or equal to those of other natural compounds such as catechins, suggesting that 1-acetyl-beta-carboline would be a good candidate in applications of the treatment of MRSA infection.

Pancreatic lipase inhibitory activity of phlorotannins isolated from Eisenia bicyclis.

Pancreatic lipase is a potential therapeutic target for the treatment of diet-induced obesity in humans. In an ongoing search for new pancreatic lipase inhibitors from natural sources, a methanolic extract of marine brown algae, Eisenia bicyclis, showed a significant inhibitory effect against pancreatic lipase. Bioassay-guided isolation of this methanolic extract using a pancreatic lipase inhibitory assay led to the isolation and identification of six known phlorotannins: eckol (1), fucofuroeckol A (2), 7-phloroeckol (3), dioxindehydroeckol (4), phlorofucofuroeckol A (5), and dieckol (6). The structures were established on the basis of nuclear magnetic resonance and mass spectrometry spectroscopic data interpretation. Among the isolated phloroglucinol polymers, compounds 2 and 3 showed potent inhibitory effects on pancreatic lipase with IC50 values ranging from 37.2 ± 2.3 to 12.7 ± 1.0 µM, respectively.

Widdrol induces cell cycle arrest, associated with MCM down-regulation, in human colon adenocarcinoma cells.

Widdrol, an odorous compound extracted from Juniperus chinensis, has been shown to inhibit the in vitro growth of in human cancer cells. This study was conducted on cultured human colon adenocarcinoma HT29 cells to elucidate the possible mechanisms by which widdrol exerts its anti-proliferative activity, which until now has remained poorly understood. It was found that widdrol induces accumulation of sub-G1 phase and arrests in the G1 phase of the cell cycle. Induction of G1 arrest by widdrol was correlated with induction of Chk2, p53 phosphorylation and CDK inhibitor p21 expression as well as inhibition of cyclin E, cyclin-dependent kinase (CDK2) and retinoblastoma protein (pRB). Moreover, mini-chromosome maintenance (MCM) proteins were markedly down-regulated in HT29 cells treated with widdrol. Altogether, these results show widdrol possesses potential anti-cancer activity against colon adenocarcinoma cells by inhibiting their proliferation and inducing cell cycle G1 arrest.

Decursin and decursinol angelate selectively inhibit NADH-fumarate reductase of Ascaris suum.

NADH-fumarate reductase (NFRD) is a key enzyme in many anaerobic helminths. Decursin and decursinol angelate have been isolated from the roots of ANGELICA GIGAS Nakai (Apiaceae) as NFRD inhibitors. They inhibited ASCARIS SUUM NFRD with IC (50) values of 1.1 and 2.7 microM, respectively. Their target is the electron transport enzyme complex I. Since the inhibitory activities of decursin against bovine heart complexes are weak, it is a selective inhibitor of the nematode complex I. In contrast, decursinol angelate moderately inhibits bovine heart complexes II and III. Decursinol inhibits A. SUUM NFRD to a similar extent, but its target is complex II. It also inhibits bovine heart complexes II and III.