Precision cardiac targeting: empowering curcumin therapy through smart exosome-mediated drug delivery in myocardial infarction.

Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.

Effect of Low Protein Diets Supplemented with Sodium Butyrate, Medium-Chain Fatty Acids, or n-3 Polyunsaturated Fatty Acids on the Growth Performance, Immune Function, and Microbiome of Weaned Piglets.

This study aimed to investigate the effects of low-protein (LP) diets supplemented with sodium butyrate (SB), medium-chain fatty acids (MCT), or n-3 polyunsaturated fatty acids (n-3 PUFA) on the growth performance, immune function, and the microbiome of weaned piglets. A total of 120 healthy weaned piglets ((Landrace × Large White × Duroc); 7.93 ± 0.7 kg initial body weight), were randomly divided into five groups. Each group consisted of six replications with four piglets per replication. Dietary treatments included control diet (CON); LP diet (LP); LP + 0.2% SB diet (LP + SB); LP + 0.2% MCT diet (LP + MCT); and LP + PUFA diet (LP + PUFA). The experimental period lasted for 4 weeks. Compared with the CON diet, LP, LP + SB, LP + MCT, and LP + PUFA diets decreased the final weight and average daily gain (ADG) of piglets (p < 0.05). There were lower (p < 0.05) concentrations of IL-8 and higher (p < 0.05) Glutathione peroxidase (GSH-Px) activity in the plasma of piglets fed with LP + SB, LP + MCT, and LP + PUFA diets than those fed with the LP diet. The piglets in the LP + SB and LP + PUFA groups had lower IKK-alpha (IKKa) mRNA expression in the colonic mucosa compared with those in the CON and LP groups (p < 0.05). The mRNA expression of TLR4 in the colonic mucosa of piglets in the LP + SB, LP + MCT, and LP + PUFA groups was decreased when compared with the CON and LP groups (p < 0.05). The LP + MCT diets increased the gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosa of piglets compared with CON, LP, and LP + SB diets (p < 0.05). The abundance of Erysipelotrichaceae in the colonic microbiome of piglets in the LP group was higher than that in the other four groups (p < 0.05). Collectively, this study showed that LP diets supplemented with SB, MCT, or n-3 PUFA reduced plasma inflammatory factor levels, increased plasma GSH-Px activity, and declined mRNA expression of TLR4 and IKKa in the colonic epithelium, whereas it reduced the abundance of Erysipelotrichaceae in the colon of piglets.

Different Fatty Acid Supplementation in Low-Protein Diets Regulate Nutrient Utilization and Lipid and Amino Acid Metabolism in Weaned Pigs Model.

This study was conducted to evaluate the effects of a low-protein (LP) diet supplemented with sodium butyrate (SB), medium-chain fatty acids (MCFAs) and n-3 polyunsaturated fatty acids (PUFAs) on nutrient utilization and lipid and amino acid metabolism in weaned pigs. A total of 120 Duroc × Landrace × Yorkshire pigs (initial body weight: 7.93 ± 0.65 kg) were randomly assigned to five dietary treatments, including the control diet (CON), LP diet, LP + 0.2% SB diet (LP + SB), LP + 0.2% MCFA diet (LP + MCFA) and LP + 0.2% n-3 PUFA diet (LP + PUFA). The results show that the LP + MCFA diet increased (p < 0.05) the digestibility of dry matter and total P in pigs compared with the CON and LP diets. In the liver of the pigs, the metabolites involved in sugar metabolism and oxidative phosphorylation significantly changed with the LP diet compared with the CON diet. Compared with the LP diet, the altered metabolites in the liver of the pigs fed with the LP + SB diet were mainly associated with sugar metabolism and pyrimidine metabolism; the altered metabolites in the liver of pigs fed with the LP + MCFA and LP + PUFA diets were mainly associated with lipid metabolism and amino acid metabolism. In addition, the LP + PUFA diet increased (p < 0.05) the concentration of glutamate dehydrogenase in the liver of pigs compared with the LP diet. Furthermore, the LP + MCFA and LP + PUFA diets increased (p < 0.05) the mRNA abundance of sterol regulatory element-binding protein 1 and acetyl-CoA carboxylase in the liver compared with the CON diet. The LP + PUFA diet increased (p < 0.05) mRNA abundances of fatty acid synthase in the liver compared with the CON and LP diets. Collectively, the LP diet supplemented with MCFAs improved nutrient digestibility, and the LP diet supplemented with MCFAs and n-3 PUFAs promoted lipid and amino acid metabolisms.

Dietary Hermetia illucens Larvae Meal Improves Growth Performance and Intestinal Barrier Function of Weaned Pigs Under the Environment of Enterotoxigenic Escherichia coli K88.

The aim of this study was to evaluate the effect of Hermetia illucens larvae meal (HI) on the growth performance and intestinal barrier function of weaned pigs. To achieve this, 72 weaned pigs [28-day-old, 8.44 ± 0.04 kg body weight (BW)] were randomly assigned to three dietary treatments: basal diet (negative control, NC), zinc oxide-supplemented diet (positive control, PC), and HI-supplemented diet [100% replacement of fishmeal (FM), HI], for 28 days in the presence of enterotoxigenic Escherichia coli (ETEC). The results showed that HI and PC increased (p < 0.05) the average daily gain (ADG) and average daily feed intake (ADFI) of weaned pigs from day 1 to 14, and decreased diarrhea incidence from day 1 to 28. Additionally, HI increased (p < 0.05) claudin-1, occludin, mucin-1 (MUC-1), and MUC-2 expression, goblet cell number, and secretory immunoglobulin A (sIgA) concentration in the intestine of weaned pigs. Compared with NC, HI downregulated (p < 0.05) interleukin-1ß (IL-1ß) and IL-8 expression, and upregulated IL-10, transforming growth factor-ß (TGF-ß), antimicrobial peptide [porcine ß defensin 1 (pBD1), pBD2, protegrin 1-5 (PG1-5)] expression in the jejunum or ileum. Moreover, HI decreased (p < 0.05) toll-like receptor 2 (TLR2), phosphorylated nuclear factor-κB (p-NF-κB), and phosphorylated mitogen-activated protein kinase (p-MAPK) expression, and increased sirtuin 1 (SIRT1) expression in the ileum. Additionally, HI increased histone deacetylase 3 (HDAC3) expression and acetylation of histone 3 lysine 27 (acH3k27) in the ileum. Furthermore, HI positively influenced the intestinal microbiota composition and diversity of weaned pigs and increased (p < 0.05) butyrate and valerate concentrations. Overall, dietary HI improved growth performance and intestinal barrier function, as well as regulated histone acetylation and TLR2-NF-κB/MAPK signaling pathways in weaned pigs.