Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma.

We aimed to study mechanisms controlling metastatic outgrowth of melanoma into clinically relevant lesions, a critical process responsible for the majority of melanoma deaths. To this end, we developed novel in vivo models and identified molecular events that can be ascribed to their distinct phenotypes, indolent or highly metastatic. Induction of a proliferative state at distant sites was associated with high levels of the stem-like/progenitor marker, SOX2, and required the upregulation of FMOD, an extracellular matrix component, which modulates tumor-stroma interactions. Functional studies revealed a possible link between FMOD and SOX2; dual FMOD and SOX2 silencing nearly abolished brain metastasis and had a similar effect on distant metastasis to other sites. Our in vitro data suggests that FMOD and SOX2 cooperation plays an important role in tumor vasculogenic mimicry. Furthermore, we found that FMOD and SOX2 functional roles might converge at the activation of transcriptional co-factors YAP and TAZ, possibly via crosstalk with the tumor suppressor Hippo pathway. Finally, high expression of both genes in patient specimens predicted early development of brain metastasis. Thus, our study identifies FMOD and SOX2 cooperation as a novel regulatory mechanism that might be linked functionally to melanoma metastatic competence.

Magnolol Supplementation Alters Serum Parameters, Immune Homeostasis, Amino Acid Profiles, and Gene Expression of Amino Acid Transporters in Growing Pigs.

This study investigated whether dietary supplementation with magnolol affects growth performance, anti-inflammatory abilities, serum and muscle amino acid profiles, and metabolisms in growing pigs. A total of 42 seventy-days-old growing barrows (Duroc × Landrace × Yorkshire) were randomly allocated into two dietary groups: Con, control group (basal diet); and Mag, magnolol group (basal diet supplemented with 400 mg/kg of magnolol). The results revealed that dietary supplementation with magnolol had no effect (p > 0.05) on growth performance. However, magnolol supplementation remarkably increased (p < 0.05) the serum content of albumin, total protein, immunoglobulin G, immunoglobulin M, and interleukin-22. In addition, dietary magnolol supplementation altered the amino acid (AA) profiles in serum and dorsal muscle and particularly increased (p < 0.05) the serum content of arginine and muscle glutamate. Simultaneously, the mRNA expression of genes associated with AA transport in jejunum (SLC38A2, SLC1A5, and SLC7A1) and ileum (SLC1A5 and SLC7A1) was higher (p < 0.05) in the Mag group than in the Con group. Additionally, the serum metabolomics analysis showed that the addition of magnolol significantly enhanced (p < 0.05) arginine biosynthesis, as well as D-glutamine and D-glutamate metabolism. Overall, these results suggested that dietary supplementation with magnolol has the potential to improve the accumulation of AAs, protein synthesis, immunity, and body health in growing pigs by increasing intestinal absorption and the transport of AAs.

Solid-state fermentation improves the quality of chrysanthemum waste as an alternative feed ingredient.

Chrysanthemum waste (CW) is an agricultural and industrial by-product produced during chrysanthemum harvesting, drying, preservation, and deep processing. Although it is nutritious, most CW is discarded, wasting resources and contributing to serious environmental problems. This work explored a solid-state fermentation (SSF) strategy to improve CW quality for use as an alternative feed ingredient. Orthogonal experiment showed that the optimal conditions for fermented chrysanthemum waste (FCW) were: CW to cornmeal mass ratio of 9:1, Pediococcus cellaris + Candida tropicalis + Bacillus amyloliquefaciens proportions of 2:2:1, inoculation amount of 6%, and fermentation time of 10 d. Compared with the control group, FCW significantly increased the contents of crude protein, ether extract, crude fiber, acid detergent fiber, neutral detergent fiber, ash, calcium, phosphorus, and total flavonoids (p < 0.01), and significantly decreased pH and saponin content (p < 0.01). SSF improved the free and hydrolyzed amino acid profiles of FCW, increased the content of flavor amino acids, and improved the amino acid composition of FCW protein. Overall, SSF improved CW nutritional quality. FCW shows potential use as a feed ingredient, and SSF helps reduce the waste of chrysanthemum processing.

Mulberry leaf extract improves intestinal barrier function and displays beneficial effects on colonic microbiota and microbial metabolism in weaned piglets.

BACKGROUND: Mulberry leaf extract (MLE) extracted from mulberry leaves is rich in a variety of bioactive ingredients and can be used as feed additives of weaned piglets. The present study was conducted to evaluate the effects of dietary MLE supplementation on intestinal barrier function, colon microbial numbers and microbial metabolites of weaned piglets. RESULTS: MLE supplementation increased the villus height and the villus height/crypt depth ratio in jejunum and ileum (P < 0.05), increased the mRNA expression of ZO-1, Claudin-1 and MUC-2 in the ileal mucosa (P < 0.05), and decreased the serum level of lipopolysaccharide (P < 0.01). Meanwhile, MLE reduced the mRNA expression of tumor necrosis factor-α and interleukin-1ß (P < 0.05) and increased secretory immunoglobulin A level in the ileal mucosa (P < 0.05). In addition, MLE increased the numbers of beneficial bacteria Bifidobacterium and Lactobacillus (P < 0.05) and decreased the number of potential pathogenic bacteria Escherichia coli (P < 0.05) in the colon. Correspondingly, MLE supplementation reduced the pH value of colonic digesta (P < 0.05) and altered the microbial fermentation pattern of the colon by increasing the concentrations of microbial metabolites derived from carbohydrates fermentation such as lactate, acetate, butyrate and total short-chain fatty acids (P < 0.05), and decreasing the concentrations of microbial metabolites derived from amino acid fermentation such as p-cresol, skatole, spermine, histamine and tryptamine (P < 0.05). CONCLUSION: MLE supplementation improved intestinal barrier function and displayed beneficial effects on colon microbes and microbial metabolism in weaned piglets. © 2022 Society of Chemical Industry.

Exogenous Glutathione Protects IPEC-J2 Cells against Oxidative Stress through a Mitochondrial Mechanism.

The accumulation of reactive oxygen species (ROS) triggers oxidative stress in cells by oxidizing and modifying various cellular components, preventing them from performing their inherent functions, ultimately leading to apoptosis and autophagy. Glutathione (GSH) is a ubiquitous intracellular peptide with multiple functions. In this study, a hydrogen peroxide (H2O2)-induced oxidative damage model in IPEC-J2 cells was used to investigate the cellular protection mechanism of exogenous GSH against oxidative stress. The results showed that GSH supplement improved the cell viability reduced by H2O2-induced oxidative damage model in IPEC-J2 cells in a dose-dependent manner. Moreover, supplement with GSH also attenuated the H2O2-induced MMP loss, and effectively decreased the H2O2-induced mitochondrial dysfunction by increasing the content of mtDNA and upregulating the expression TFAM. Exogenous GSH treatment significantly decreased the ROS and MDA levels, improved SOD activity in H2O2-treated cells and reduced H2O2-induced early apoptosis in IPEC-J2 cells. This study showed that exogenous GSH can protect IPEC-J2 cells against apoptosis induced by oxidative stress through mitochondrial mechanisms.

Effects of dietary citrus extract on growth performance, carcass characteristics and meat quality of pigs.

This study investigated the effects of citrus extract on growth, carcass and meat quality of Duroc × Landrace × Large White pigs. One hundred and eight pigs (54 barrows, 54 females) were assigned to one of three dietary treatments for 138 days. The dietary treatments were (1) basic diet; (2) basic diet supplemented with 75 mg/kg chlortetracycline; and (3) basic diet supplemented with citrus extract (0.25 ml/kg during 56-112 days of age and 0.20 ml/kg during 113-194 days of age). No significant differences among treatments were found for growth performance, carcass characteristics, meat quality and free amino acids (p > 0.05). Feeding citrus extract tended to increase intramuscular fat (p = 0.052). Citrus extract and chlortetracycline increased C15:0 concentration (p = 0.016) and superoxide dismutase activity (p = 0.004). The pigs that received chlortetracycline exhibited the lowest (p = 0.033) muscle malondialdehyde concentration. Overall, citrus extract ameliorated some meat quality indicators without adverse effects on pig growth or carcass performance.

Dietary supplementation with citrus extract alters the plasma parameters, circulating amino acid profiles and gene expression of small intestinal nutrient transporters in Chinese yellow-feathered broilers.

BACKGROUND: This study evaluated the effects of citrus extract (CE) on growth performance, plasma amino acid (AA) profiles, intestinal development and small intestine AA and peptide transporter expression levels in broilers. A total of 540 one-day-old yellow-feathered broilers were fed a basal diet without any antibiotic (control group), or a basal diet containing 10 mg kg-1 zinc bacitracin (antibiotic group), or a basal diet supplemented with 10 mg kg-1 CE (CE group). After 63 days of feeding, two broilers per pen were slaughtered to collect tissues for further analysis. RESULTS: Results showed that CE increased (P < 0.05) the final body weight and average daily gain from day 1 to 63, and decreased (P < 0.05) the feed/gain ratio from day 1 to 63. Dietary CE supplementation increased (P < 0.05) plasma total protein, albumin and glucose concentration, and decreased (P < 0.05) urea concentration. CE supplementation increased (P < 0.05) the villus height in the ileum and the villus height/crypt depth in the jejunum and ileum, but decreased (P < 0.05) the crypt depth in the jejunum and ileum. CE supplementation increased (P < 0.05) most plasma essential AA concentrations. Additionally, CE supplementation upregulated (P < 0.05) ASCT1, b0,+ AT, B0 AT1, EAAT3, rBAT, y+ LAT2 and PepT1 expression in the jejunum, and b0,+ AT, EAAT3, rBAT, y+ LAT2, CAT1 and PepT1 in the ileum. CONCLUSIONS: Collectively, our results indicated that CE supplementation promotes intestinal physiological absorption of AAs by upregulating gene expression of small intestinal key AA and peptide transporters, thereby enhancing the growth performance of broilers. © 2020 Society of Chemical Industry.

Chlorogenic acid: A comprehensive review of the dietary sources, processing effects, bioavailability, beneficial properties, mechanisms of action, and future directions.

Chlorogenic acids (CGAs), a group of hydroxycinnamates, are generally abundant in everyday foods and beverages, most prominently in certain coffee drinks. Among them, the chlorogenic acid (CGA), also termed as 5-O-caffeoylquinic acid (5-CQA), is one of the most abundant, highly functional polyphenolic compounds in the human diet. The evidence of its health benefits obtained from clinical studies, as well as basic research, indicates an inverse correlation between 5-CQA consumption and a lower risk of metabolic syndromes and chronic diseases. This review focuses on the beneficial properties for health and mechanisms of action of 5-CQA, starting with its history, isomers, dietary sources, processing effects, preparation methods, pharmacological safety evaluation, and bioavailability. It also provides the possible molecular mechanistic bases to explain the health beneficial effects of 5-CQA including neuroprotective, cardiovascular protective, gastrointestinal protective, renoprotective, hepatoprotective, glucose and lipid metabolism regulatory, and anticarcinogenic effects. The information summarized here could aid in the basic and clinical research on 5-CQA as a natural dietary additive, potential drug candidate, as well as a natural health promoter.

Effect of amino acids and their derivatives on meat quality of finishing pigs.

Amino acids provide key nutritional value, and significantly contribute to taste and flavor of meat. Here, we review the role of free amino acids in the muscle fibers in meat quality and sensory signals. We furthermore discuss how dietary supplementation of free amino acids and their derivatives (e.g. tryptophan, threonine, arginine, lysine, leucine, glutamate, threonine, sarcosine, betaines, and cysteamine) can influence these attributes. The available data shows that the quality of the meat is subject to the amino acids that are provided in the animal feed.

Lactobacillus reuteri LR1 Improved Expression of Genes of Tight Junction Proteins via the MLCK Pathway in IPEC-1 Cells during Infection with Enterotoxigenic Escherichia coli K88.

Intestinal epithelial barrier damage disrupts immune homeostasis and leads to many intestinal disorders. Lactobacillus reuteri strains have probiotic functions in their modulation of the microbiota and immune system in intestines. In this study, the effects of L. reuteri LR1, a new strain isolated from the feces of weaning piglets, on intestinal epithelial barrier damage in IPEC-1 cells caused by challenge with enterotoxigenic Escherichia coli (ETEC) K88 were examined. It was found that L. reuteri LR1, in large part, offset the ETEC K88-induced increase in permeability of IPEC-1 cell monolayers and decreased the adhesion and invasion of the coliform in IPEC-1 cells. In addition, L. reuteri LR1 increased transcript abundance and protein contents of tight junction (TJ) proteins zonula occluden-1 (ZO-1) and occludin in ETEC K88-infected IPEC-1 cells, whereas it had no effects on claudin-1 and F-actin expression. Using colloidal gold immunoelectron microscopy, these effects of L. reuteri LR1 on ZO-1 and occludin content in IPEC-1 cells were confirmed. By using ML-7, a selective inhibitor of myosin light-chain kinase (MLCK), the beneficial effect of L. reuteri LR1 on contents of ZO-1 and occludin was shown to be dependent on the MLCK pathway. In conclusion, L. reuteri LR1 had beneficial effects on epithelial barrier function consistent with increasing ZO-1 and occludin expression via a MLCK-dependent manner in IPEC-1 cells during challenge with ETEC K88.