Immunomodulatory Antibacterial Hydrogel for Wound Infection Management.

Background: Wound healing has always been a focal point in clinical work. Bacterial infections and immune microenvironment disorders can both hinder normal wound healing. Current wound dressings only serve a covering function. Developing wound dressings with antibacterial and immunomodulatory functions is crucial for aiding wound healing. To address this issue, we have developed a hydrogel with antibacterial and immunomodulatory functions for managing infected wounds. Methods: The present study describes a photo-crosslinked antibacterial hydrogel composed of curcumin, silver nanoparticles-loaded reduced graphene oxide, and silk fibroin methacryloyl for the treatment of infected wounds. The study assessed its antibacterial properties and its capacity to induce macrophage M2 polarization through in vitro and in vivo experiments. Results: The hydrogel demonstrates robust antibacterial properties and enhances macrophage M2 polarization in both in vitro and in vivo settings. Moreover, it accelerates the healing of infected wounds in vivo by stimulating collagen deposition and angiogenesis. Conclusion: Overall, this hydrogel shows great potential in managing wound infections.

Effect of Ornithine α-Ketoglutarate on Intestinal Microbiota and Serum Inflammatory Cytokines in Dextran Sulfate Sodium Induced Colitis.

Ornithine α-ketoglutarate (OKG), a nutritional compound, is an amino acid salt with anti-oxidative and anti-inflammatory effects on humans and animals. Ulcerative colitis (UC), as an inflammatory bowel disease (IBD), leads to chronic intestinal inflammatory dysfunction. This study evaluated the optimal dosage of OKG in healthy mice. Then, a mouse model of acute colitis was established using dextran sodium sulfate (DSS), and the preventive effect of OKG on DSS-induced colitis in mice was explored through analysis of serum inflammatory cytokines and fecal microbiota. Initially, the mice were randomly divided into a control group, a group given a low dose of OKG (LOKG: 0.5%), a group given a medium dose of OKG (MOKG: 1%), and a group given a high dose of OKG (HOKG: 1.5%); they remained in these groups for the entire 14-day experimental period. Our results demonstrated that 1% OKG supplementation increased body weight, serum growth hormone (GH), insulin (INS), alkaline phosphatase (ALP), Tyr, and His and decreased urea nitrogen (BUN), NH3L, and Ile. Then, a 2 × 2 factor design was used for a total of 40 mice, with diet (a standard diet or a 1% OKG diet) and challenge (4% DSS or not) as the main factors. During days 14 to 21, the DSS mice were administered 4% DSS to induce colitis. The results revealed that OKG alleviated weight loss and reversed the increases in colonic histological damage induced by DSS. OKG also increased serum IL-10 secretion. Moreover, OKG enhanced the abundance of Firmicutes and decreased that of Bacteriodetes at the phylum level and particularly enhanced the abundance of Alistipes and reduced that of Parabacterioides at the genus level. Our results indicated that OKG promotes growth performance and hormone secretion and regulates serum biochemical indicators and amino acid concentrations. Furthermore, 1% OKG supplementation prevents DSS-induced colitis in mice via altering microbial compositions and reducing the secretion of inflammatory cytokines in serum.

Comparison of the meat quality and fatty acid profile of muscles in finishing Xiangcun Black pigs fed varied dietary energy levels.

To study the effects of dietary energy level on the meat quality of different muscles in finishing pigs, 400 Xiangcun Black pigs (BW = 79.55 ± 4.77 kg) were randomly assigned to 5 treatments with varied calculated digestive energy (DE) at 3,050, 3,100, 3,150, 3,200 and 3,250 kcal/kg, respectively. Each treatment had 8 replicates with 10 pigs per replicate. Meat quality, amino acid and fatty acid composition were tested in this study. No differences in average daily gain, average daily feed intake or feed-to-gain ratio (P > 0.05) were observed among dietary treatments. Glycogen concentrations of longissimus dorsi (LD) muscle in DE3150 was higher than those in other groups (P < 0.05). The crude fat concentration of biceps femoris (BF) muscle in DE3250 tended to be higher than that in DE3150 and DE3100 groups (P < 0.05). Pigs in DE3250 and DE3200 had higher fiber density and smaller cross-sectional area of BF muscle than those in DE3150 (P < 0.05). Pigs in DE3150 had the highest Cu concentration in LD muscle compared with those in DE3200, DE3250 (P < 0.05). The C16:1 proportion of LD muscle was lower (P < 0.01) and C20:1 was higher (P < 0.05) in DE3050 than that in the other dietary treatments. The C18:3n6 and C20:3n6 proportions of BF muscle in DE3150 were higher than those in DE 3050, DE3200 and DE3250 (P < 0.05). For LD muscle, mRNA expressions of type I and IIa MyHC in group DE3150 were higher than other treatments (P < 0.01). The LD muscle in DE3150 expressed higher PPARd than in other groups (P < 0.01). Pigs in DE3100 expressed higher FOX1 than in DE3200 and DE3250 (P < 0.05). Sterol-regulatory element binding proteins (SREBPa) mRNA expression decreased linearly when dietary energy level increased in BF muscle (P < 0.01). In conclusion, a 200 kcal/kg decrease in digestible energy for 4 consecutive weeks did not affect growth performance of Xiangcun Black pigs. Furthermore, LD and BF muscle respond differently to dietary energy level, and meat quality was improved by the medium energy level during the finishing phase.

Ornithine α-Ketoglutarate Alleviates Inflammation via Regulating Ileal Mucosa Microbiota and Metabolites in Enterotoxigenic Escherichia coli-Infected Pigs.

Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of diarrhea in weaned piglets, and ornithine α-ketoglutarate (OKG) as a food supplement has been shown to improve intestinal immune status in animals and humans. However, it remains unknown whether OKG alleviates inflammation through the regulation of gut microbiota and its metabolites on ETEC-infected piglets. This study was conducted to explore the impact of OKG on growth performance, immunity, and ileal mucosa microbiota and its metabolites in piglets infected with ETEC. On a total of 40 pigs, a 2 × 2 factor design was performed; the major factors were diet (basal diet or 1% OKG diet) and challenge (E. coli or LB Broth). The results showed that ETEC-infection inhibited growth performance, and OKG supplementation alleviated growth performance. Interestingly, ETEC-infection increased the serum TNF-α and IL-6, decreased the serum IL-10, downregulated the mRNA expression of IL-1ß, IL-6, MyD88, and improved the mRNA expression of IL-8, IL-18, and TLR4. OKG inhibited serum IL-6, suppressed the phosphorylation of downstream signals of NF-κB/JNK in the ileum, and enhanced serum IL-10 and ileum SIgA in ETEC-challenged piglets. OKG supplementation enhanced the mRNA expression of IL-1ß and IL-10 and reduced NF-κB and MyD88 in the ileum. Importantly, OKG reversed intestinal microbiota dysfunction, including the diversity of ileal microbiota, the relative abundances of Actinobacillus, Turicibacter, and [Acetivibrio]_ethanolgignens_group, which significantly affected arachidonic acid metabolism and primary bile acid biosynthesis. Collectively, our results suggest that OKG improves growth performance, regulates immunity, and ileal mucosa microbiota and its metabolites in ETEC-infected piglets.

Circadian rhythms and obesity: Timekeeping governs lipid metabolism.

Almost all living organisms have evolved autoregulatory transcriptional-translational feedback loops that produce oscillations with a period of approximately 24-h. These endogenous time keeping mechanisms are called circadian clocks. The main function of these circadian clocks is to drive overt circadian rhythms in the physiology of the organisms to ensure that main physiological functions are in synchrony with the external environment. Disruption of circadian rhythms caused by genetic or environmental factors has long-term consequences for metabolic health. Of relevance, host circadian rhythmicity and lipid metabolism are increasingly recognized to cross-regulate and the circadian clock-lipid metabolism interplay may involve in the development of obesity. Multiple systemic and molecular mechanisms, such as hormones (ie, melatonin, leptin, and glucocorticoid), the gut microbiome, and energy metabolism, link the circadian clock and lipid metabolism, and predictably, the deregulation of circadian clock-lipid metabolism interplay can increase the risk of obesity, which in turn may exacerbate circadian disorganization. Feeding time and dietary nutrients are two of key environmental Zeitgebers affecting the circadian rhythm-lipid metabolism interplay, and the influencing mechanisms in obesity development are highlighted in this review. Together, the characterization of the clock machinery in lipid metabolism aimed at producing a healthy circadian lifestyle may improve obesity care.

Effects of ornithine α-ketoglutarate on growth performance and gut microbiota in a chronic oxidative stress pig model induced by d-galactose.

The aim of this study was to evaluate the protective effects and underlying mechanisms of ornithine α-ketoglutarate (OKG) on d-galactose (d-gal)-induced chronic oxidative stress in a pig model. A total of 40 castrated young pigs were randomly separated into five groups, including a control group, a model group treated with 5 mg per kg body weight (BW) d-gal, and three d-gal + OKG groups in which the pigs received 0.5%, 1%, and 2% OKG (n = 8). The experiment lasted for 28 days. The growth performance, serum oxidative stress index, expression of relative intestinal genes, gut microbiota, and serum amino acid pool were determined. The results demonstrated that administration of d-gal significantly affected growth performance and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels including related mRNA expression suppression, malondialdehyde (MDA) levels enhancement, gut microbiota dysfunction, and serum amino acid alteration in pigs. However, treatment with 0.5% OKG markedly ameliorated the reduction in the growth performance, as evidenced by the reversed final body weight, average feed intake, and average body weight. Also, 0.5% OKG enhanced the SOD and GSH-Px levels including relative mRNA expression in the intestine and inhibited lipid oxidation subsequent to MDA generation. The intestinal abundances of Firmicutes were increased and those of Proteobacteria, Fusobacteria, Bacteriodetes, and Euryarchaeota were decreased in the pigs supplemented with 0.5% OKG. Meanwhile, 0.5% OKG increased the glutamate, proline, aspartate, threonine, valine, isoleucine and leucine levels in the serum. Collectively, these results indicate that d-gal induced chronic oxidative stress and also proved the positive effects of 0.5% OKG on altering the pig gut microbe, restoring serum amino acid and alleviating the growth-suppression induced by d-gal chronic oxidative stress.

Supplementation with α-ketoglutarate to a low-protein diet enhances amino acid synthesis in tissues and improves protein metabolism in the skeletal muscle of growing pigs.

α-Ketoglutarate (AKG) is a crucial intermediate in the tricarboxylic acid (TCA) cycle and can be used for the production of ATP and amino acids in animal tissues. However, the effect of AKG on the expression patterns of genes involved in muscle protein metabolism is largely unknown, and the underlying mechanism remains to be elucidated. Therefore, we used young pigs to investigate the effects of a low crude protein (CP) diet and a low CP diet supplemented with AKG on protein accretion in their skeletal muscle. A total of 27 growing pigs with an initial body weight of 11.96 ± 0.18 kg were assigned randomly to one of the three diets: control (normal recommended 20% CP, NP), low CP (17% CP, LP), or low CP supplemented with 1% AKG (ALP). The pigs were fed their respective diets for 35 days. Free amino acid (AA) profile and hormone levels in the serum, and the expression of genes implicated in protein metabolism in skeletal muscle were examined. Results showed that compared with the control group or LP group, low-protein diets supplemented with AKG enhanced serum and intramuscular free AA concentrations, the mRNA abundances of AA transporters, and serum concentrations of insulin-like growth factor-1 (IGF-1), activated the mammalian target of rapamycin (mTOR) pathway, and decreased serum urea concentration and the mRNA levels for genes related to muscle protein degradation (P < 0.05). In conclusion, these results indicated that addition of AKG to a low-protein diet promotes amino acid synthesis in tissues and improves protein metabolism in skeletal muscle.